His voice matured as he left his teens, around the time of ska's transition to rocksteady and this period in the late 1960s produced many hits including one of the first rocksteady records, "Dancing Mood", "Jerk in Time" (with the Wailers), "Feel Good All Over", "I'm Not a King", "True Believer in Love", "Rain From the Skies", "Conquer Me" and "Riding For A Fall". "Won't You Come Home", a duet with Ken Boothe on a rhythm originally cut by The Conquerors for Sonia Pottinger has become one of the most-versioned Jamaican tracks ever. After leaving Studio One he recorded for numerous other producers, with varying degrees of success, and set up his own short-lived W&C label along with Wilburn Cole, and the similarly-fated Links label with Ken Boothe, The Gaylads and The Melodians. He enjoyed success with Bunny Lee in the late 1960s and early 1970s with tracks such as "This Old Heart of Mine", "Footsteps of Another Man", and "Better Must Come". His double A-side "It Hurts"/"Put Yourself in My Place" was a skinhead favourite and narrowly missed UK chart success. He recorded a version of "Run Run", a song he had originally recorded for Dodd, for maverick producer Keith Hudson.

1970 saw Wilson's first tour of the UK, where he also recorded a number of songs for the Trojan record label.

In 1972, Michael Manley's People's National Party chose Wilson's "Better Must Come" as their election campaign song. The same year saw the release of one of his most popular songs, "Cool Operator", which became his nickname. He worked with a string of producers in the years that followed, including Joe Gibbs ("Mash Up Illiteracy", "Pretty Girl"), Gussie Clarke ("Love"), Winston "Niney" Holness ("Rascal Man"), Harry J ("Ask The Lonely"), and Joseph Hoo Kim ("It's a Shame").

In 1976, he recorded a cover of The Wailers' "I'm Still Waiting" for Lloyd Charmers, which was hugely popular, and enjoyed some cross-over success, and was followed by the album Sarge, which is considered one of his strongest. Also a Bob Andy produced song, "The Last Thing On My Mind" rose to number one in Jamaica. Wilson continued the run of success until the end of the decade, but his career floundered during the early 1980s, with releases less common. His fortunes revived in the digital age with releases for King Jammy ("Don't Put The Blame On Me") and Bunny Lee ("Ease Up"), with new albums following, but he again drifted out of the limelight, with his health declining, and is best remembered for his earlier work.

In 1994, Wilson's enduring legacy to Jamaican music was recognized by a special plaque awarded him by the Jamaican government, and presented by the then Prime Minister, Patterson.

Delroy Wilson died on 6 March 1995 at Kingston's UWI hospital, of complications from cirrhosis of the liver. He was 46 years old.

Delroy is referenced by The Clash, in "(White Man) In Hammersmith Palais".

Wilson's work has also been collected on over 15 'Best of' compilations and he features on dozens of compilations of reggae and ska music.