Jimmy Iovine, CEO of Interscope Records, requested a demo tape of Eminem's after he placed second at the 1997 Rap Olympics. Eminem had also won Wake Up Show's "Freestyle Performer of the Year" award, helping him acquire a record deal. Iovine played the tape for record producer Dr. Dre, founder of Aftermath Entertainment. The two began recording tracks for Eminem's upcoming major-label debut The Slim Shady LP, and Eminem made a guest performance on the album Devil Without a Cause by Kid Rock. Hip-hop magazine The Source featured Eminem in its "Unsigned Hype" column in March 1998.

The Slim Shady EP was a debut extended play by Eminem, published by Web Entertainment in 1997. The Slim Shady EP was released on cassette, vinyl, and CD. The vinyl and CD versions were released in 1998. Eminem first introduced his "Slim Shady" persona on this EP, and his lyrics are a marked departure from those found on Infinite, featuring constant references to drug use, sexual acts, mental instability, and over-the-top violence. Another departure was his exploration of more serious themes of dealing with poverty, his direct and self-deprecating response to criticism, and of marital and family difficulties. His flow is also noticeably different than on Infinite; whereas critics claimed he sounded too much like Nas and AZ on that album. Eminem also began utilizing story telling on this EP. The production value of the music on the tracks — from previous collaborators DJ Head, The Bass Brothers, and Mr. Porter — was also noticeably higher than on prior album efforts. According to Billboard, at this point in his life Eminem had "realized his musical ambitions were the only way to escape his unhappy life".

After being signed to Aftermath Entertainment/Interscope Records in 1998, Eminem released his first major studio album, The Slim Shady LP, heavily based on the production by Dr. Dre, one year later in 1999. Billboard praised the album as "light years ahead of the material he had been writing beforehand". It went on to be one of the most popular albums of 1999, going triple platinum by the end of the year. With the album's popularity came controversy surrounding many of the album's lyrics. In "'97 Bonnie and Clyde", he describes a trip with his infant daughter, disposing of his wife's body. Another song, "Guilty Conscience", ends with his encouraging a man to murder his wife and her lover. "Guilty Conscience" marked the beginning of the friendship and musical bond that Dr. Dre and Eminem would share. The two label-mates would later collaborate on a line of hit songs, including "Forgot About Dre" and "What's the Difference" from Dr. Dre's album 2001, "Bitch Please II" from The Marshall Mathers LP, "Say What You Say" from The Eminem Show, "Encore/Curtains Down" from Encore and "Old Time's Sake" and "Crack a Bottle" from Relapse. Dr. Dre would go on to make at least one guest appearance on all of Eminem's studio albums under the label Aftermath. The album has now been certified 4× platinum by the RIAA. With the release of it, Eminem was accused of imitating the style and subject matter of underground rapper Cage.

The Marshall Mathers LP was released in May 2000. It went on to sell 1.76 million copies in its first week, breaking the records set by Snoop Dogg's Doggystyle as the fastest-selling hip hop album and Britney Spears' ...Baby One More Time as the fastest-selling solo album in United States history. The first single released from the album, "The Real Slim Shady", was a success and created some controversy by insulting celebrities and making dubious claims about them; he states, among other things, that Christina Aguilera performed oral sex on Fred Durst and Carson Daly. In his second single, "The Way I Am", he reveals to his fans the pressures from his record company to top "My Name Is" and sell more records. Although Eminem had parodied shock rocker Marilyn Manson in the video "My Name Is", the artists are reportedly on good terms; Manson is name-dropped in "The Way I Am" and also appeared in its music video, as well as performing a remix of the song with Eminem in concert. In the third single, "Stan" (which samples Dido's "Thank You"), Eminem attempts to deal with his new-found fame, taking on the persona of a deranged fan who kills himself and his pregnant girlfriend, mirroring "'97 Bonnie & Clyde" on The Slim Shady LP. In the music video of "Stan", Eminem was shown writing with his left hand, ending the fan debate over his dominant hand. Q magazine named "Stan" the third-greatest rap song of all time, and the song came tenth in a similar survey conducted by Top40-Charts.com. The song has since become highly acclaimed and was ranked 290th in Rolling Stone magazine's "500 Greatest Songs of All Time" list. In July 2000, Eminem became the first white person to be featured on the cover of The Source magazine. This album has been certified 10× Platinum by the RIAA.

Eminem performed with Elton John at the 43rd Grammy Awards ceremony in 2001; the Gay & Lesbian Alliance Against Defamation (GLAAD), an organization that perceived Eminem's lyrics to be homophobic, condemned the openly gay John's decision to perform with Eminem. Entertainment Weekly put it on its end-of-the-decade, "best-of" list, saying, "It was the hug heard 'round the world. Eminem, under fire for homophobic lyrics, shared the stage with a gay icon for a performance of "Stan" that would have been memorable in any context." On February 21, the day of the ceremony, GLAAD held a protest outside the Staples Center, the venue where the Grammy ceremony was held. Music tours that he participated in for 2001 included the Up in Smoke Tour with rappers Dr. Dre, Snoop Dogg, Xzibit, and Ice Cube, the Family Values Tour with the band Limp Bizkit, and headlining the Anger Management Tour with Papa Roach, Ludacris, and Xzibit.

Eminem's third major album, The Eminem Show, was released in summer 2002 and proved to be another hit for the rapper reaching number one on the charts and selling well over 1.332 million copies in its first full week sales. It featured the single "Without Me", in which he makes derogatory comments about boy bands, Limp Bizkit, Dick Cheney and Lynne Cheney, and Moby, among others. The Eminem Show has been certified 10× Platinum by the Recording Industry Association of America (RIAA). The album reflected on the impact of his rise to fame, his relationship with his wife and daughter, and his status in the hip-hop community. He also addresses the charges he faced over assaulting a bouncer he saw kissing his wife in 2000. Stephen Thomas Erlewine of Allmusic felt that while there was clear anger present on several tracks, this album was considerably less inflammatory than The Marshall Mathers LP. However, L. Brent Bozell III, who previously criticized The Marshall Mathers LP for perceived misogynistic lyrics in the album, noted The Eminem Show for its extensive use of obscene language, giving Eminem the nickname "Eminef" for the bowdlerization of motherfucker, an obscenity prevalent in the album. The Eminem Show was the best-selling album of 2002.

On December 8, 2003, the United States Secret Service admitted it was "looking into" allegations that Eminem had threatened the President of the United States. The lyrics in question: "Fuck money/I don't rap for dead presidents/I'd rather see the president dead/It's never been said, but I set precedents ..." The song in question, "We As Americans", wound up on a bonus CD accompanying the album.

In 2004, Eminem released his fourth major album, Encore. The album was another chart-topper, as it was driven by the single "Just Lose It", notable for being disrespectful towards Michael Jackson. On October 12, 2004, a week after the release of "Just Lose It", Eminem's first single from Encore, Michael Jackson called into the Los Angeles-based Steve Harvey radio show to report his displeasure with the video, which parodies Jackson's child molestation trial, plastic surgery, and an incident in which Jackson's hair caught on fire while filming a Pepsi commercial in 1984. The lyrics to "Just Lose It" refer to Jackson's legal troubles, however he does state in his song "... and that's not a stab at Michael/That's just a metaphor/I'm just psycho...." Many of Jackson's supporters and friends spoke out about the video, including Stevie Wonder, who called the video "kicking a man while he's down" and "bullshit", and Steve Harvey, who declared, "Eminem has lost his ghetto pass. We want the pass back." In the video, Eminem parodied Pee-wee Herman, MC Hammer, and "Blond Ambition"-era Madonna. Regarding Jackson's protest, "Weird Al" Yankovic, who parodied the Eminem song "Lose Yourself" on a track titled "Couch Potato" on his 2003 album Poodle Hat, told the Chicago Sun-Times, "Last year, Eminem forced me to halt production on the video for my "Lose Yourself" parody because he somehow thought that it would be harmful to his image or career. So the irony of this situation with Michael is not lost on me." Black Entertainment Television was the first channel to stop airing the video. MTV, however, announced it would continue airing the video. The Source, through its CEO Raymond "Benzino" Scott, wanted not only the video to be pulled, but the song off the album, and a public apology to Jackson from Eminem. In 2007 Jackson and Sony bought Famous Music LLC from Viacom. This deal gave him the rights to songs by Eminem, Shakira and Beck, among others.

Despite the comedic theme of the lead single, Encore had its fair share of serious subject matter, including the anti-war track "Mosh". On October 25, 2004, a week before the 2004 US Presidential election, Eminem released the video for "Mosh" on the Internet. The song was strongly critical of President George W. Bush, with lyrics such as "fuck Bush" and "this weapon of mass destruction that we call our president". The video features Eminem gathering up an army of people, including rapper Lloyd Banks, presented as victims of the Bush administration, and leading them to the White House. However, once the army breaks in, it is revealed that they are there to simply register to vote, and the video ends with the words "VOTE Tuesday November 2" on the screen. After Bush was re-elected, the video's ending was changed to Eminem and the protesters invading while Bush was giving a speech.

In 2005, some industry insiders speculated that Eminem was considering ending his rapping career after six years and several multi-platinum albums. Speculation began in early 2005 about a double-disc album to be released late that year, rumored to be titled The Funeral. The album later manifested itself as a greatest hits album under the name Curtain Call: The Hits in December. In July 2005, the Detroit Free Press broke news of a potential final bow for Eminem as a solo performer, quoting members of his inside circle who said that he would begin to fully embrace the role of producer and label executive. On the same day of the release of the compilation album, Eminem denied that he was retiring on Detroit-based WKQI's "Mojo in the Morning" radio show, but implied that he would at least be taking a break as an artist, saying "I'm at a point in my life right now where I feel like I don't know where my career is going ... This is the reason that we called it 'Curtain Call', because this could be the final thing. We don't know." He released The Re-Up with the members of his record label, Shady Records. It was released in 2006.

In 2005, Eminem was a subject of Bernard Goldberg's book, 100 People Who Are Screwing Up America; he ranked No. 58. Goldberg cited a 2001 column by Bob Herbert of The New York Times claiming, "In Eminem's world, all women are whores and he is eager to rape and murder them." Goldberg cited Eminem's song "No One's Iller" from The Slim Shady EP as an example of misogyny in his music. In summer 2005, Eminem embarked on his first US concert run in three years, the Anger Management 3 Tour, featuring 50 Cent, G-Unit, Lil Jon, D12, Obie Trice, The Alchemist, and others. In August 2005, Eminem canceled the European leg of the tour and subsequently announced that he had entered drug rehabilitation for treatment for a "dependency on sleep medication". Curtain Call: The Hits was released on December 6, 2005, under Aftermath Entertainment. In its first week it sold nearly 441,000 copies in the US and was Eminem's fourth straight No. 1 album on the Billboard Hot 200. The album has been certified 2× Platinum by the RIAA.

In September 2007, Eminem called into New York radio station Hot 97 during an interview with 50 Cent and said he was "in limbo" and "debating" about when and if he would release another album. He said, "I'm always working – I'm always in the studio. It feels good right now, the energy of the label. For a while, I didn't want to go back to the studio ... I went through some personal things. I'm coming out of those personal things it feels good."

Eminem made an appearance on his Sirius channel Shade 45 in September 2008 in which he said, "Right now I'm kinda just concentrating on my own stuff, for right now and just banging out tracks and producing a lot of stuff. You know, the more I keep producing the better it seems like I get 'cause I just start knowing stuff." It was around this time that Interscope finally confirmed the existence of a new Eminem album, with Spring 2009 later being stated as the period span in which the album is due. In December 2008, he gave more details on the album, which he recently reported was being titled Relapse. He said, "Me and Dre are back in the lab like the old days, man. Dre will end up producing the majority of the tracks on 'Relapse'. We are up to our old mischievous ways ... let's just leave it at that."

On March 5, 2009, Eminem reported in a press release that he would be releasing two new albums that year. Relapse, the first album, was released on May 19, while "We Made You", the first official single and its music video, were released on April 7. While Relapse did not manage to sell as well as Eminem's previous efforts, it was still a commercial success that received some critical acclaim, while also re-establishing his presence in the hip hop world. Relapse was named one of the top albums of 2009. Relapse has sold more than five million copies worldwide. During the 2009 MTV Movie Awards, Sacha Baron Cohen descended upon the audience wearing an angel's costume and landed on top of Eminem with his buttocks facing towards Eminem's face, resulting in Eminem storming out of the awards ceremony in disgust. Three days later, Eminem stated it was a staged act that they had planned together. On October 30, Eminem performed at the Voodoo Music Experience in New Orleans as a headliner in his first full performance in 2009. The performance included several songs from Relapse, as well as many of Eminem's older hits and an appearance by D12. On November 19, Eminem announced on his website that Relapse: Refill would be released on December 21. The album was a re-release of the Relapse album with seven bonus tracks, including "Forever" and "Taking My Ball". In a statement he described the forthcoming CD:

"I want to deliver more material for the fans this year like I originally planned ... Hopefully these tracks on The Refill will tide the fans over until we put out Relapse 2 next year ... I got back in with Dre and then a few more producers, including Just Blaze, and went in a completely different direction which made me start from scratch. The new tracks started to sound very different than the tracks I originally intended to be on Relapse 2, but I still want the other stuff to be heard. "

On April 14, 2010, Eminem tweeted, "There is no Relapse 2", to his followers. This caused people to believe that he was not releasing an album at all, but it simply meant that the album title would be changed to Recovery. He confirmed this by tweeting, "RECOVERY", with a link to his website. Eminem said, "I had originally planned for Relapse 2 to come out last year. But as I kept recording and working with new producers, the idea of a sequel to Relapse started to make less and less sense to me, and I wanted to make a completely new album. The music on Recovery came out very different from Relapse, and I think it deserves its own title." His seventh studio album, Recovery, was released on June 18. In the US, Recovery sold 741,000 in its first week to land atop the Billboard 200. It became Eminem's sixth consecutive number-one album in the US and achieved international commercial success, charting at number one in several other countries. It stayed at number-one on the US Billboard 200 chart for five consecutive weeks and a total of seven weeks. Recovery was reported by Billboard to be the best-selling album of 2010, making Eminem the first artist in Nielsen SoundScan history to have two year-end best-selling albums. Recovery is the best selling digital album in history. The first single, "Not Afraid", was released on April 29, and debuted at number one on the Billboard Hot 100. The music video was released on June 4. "Not Afraid" was followed by a second single, "Love the Way You Lie," which debuted at number 2 and then rose to the top. "Love the Way You Lie" was the best-selling single of 2010 in the United Kingdom even though it did not reach number 1 there, this is the first time this has happened in the UK since 1969. Despite some criticism towards its consistency, Recovery received positive reviews from most music critics. As of November 21, 2010 (2010-11-21), the album had sold three million copies in the US. Recovery was also named the best selling album worldwide of 2010 joining The Eminem Show, which was the best seller of 2002 giving him two worldwide year end number one albums. With Recovery, Eminem achieved the record for most successive US No.1 albums by a solo artist.

Eminem appeared at the 2010 BET Awards, performing "Not Afraid" and "Airplanes, Part II", with B.o.B. He also performed at the Activison E3 concert. In June 2010, Eminem and Jay-Z announced they would perform together in a pair of concerts in Detroit and New York. The event was dubbed The Home & Home Tour. The first two concerts rapidly sold out, prompting the scheduling of an additional show at each venue. BET also named Eminem the number one rapper of the 21st century. Eminem opened the 2010 MTV Video Music Awards on September 12, 2010, by performing "Not Afraid" and "Love the Way You Lie", with Rihanna performing the chorus. Due to the success of Recovery and the Home & Home Tour, he was named the 2010 Hottest MC in the Game by MTV and "Emcee of the Year" by hip hop news website HipHopDX. Eminem and Rihanna collaborated once again to make "Love the Way You Lie (Part II)", the sequel to their hit single "Love the Way You Lie". Rihanna is the lead singer, as opposed to Eminem being the main vocals in the original "Love the Way You Lie". The song is said to be from the female perspective. In December 2010, in Billboard's "The Top 25 Music Moments of 2010", The "Great Eminem Recovery" was named the number one music moment of 2010. Eminem appeared at the 2011 Grammy Awards on February 13, 2011, performing "Love the Way You Lie (Part II)" with Rihanna and Adam Levine, and "I Need a Doctor" with Dr. Dre and Skylar Grey. In February 2011, it was announced that "Space Bound" would be released as the fourth single from Recovery along with a music video for the song which was shot with former porn star Sasha Grey. The long-awaited video was released on June 24 on the iTunes Store.

In 2010, Eminem started collaborating with Writer's Block' with