Originally from South Wimbledon, London, England, he moved with his family to The Bronx in 1975 where he met Dana Dane, later forming a hip hop duo as Kangol Crew. Rick's characteristic eyepatch was acquired after being blinded in the right eye by broken glass as an infant. He is best known for a series of rap recordings during the 1980s, including "Hey Young World", "Children's Story" and "La Di Da Di", B-side of Doug E. Fresh single "The Show" (1985). Once he gained a degree of wealth, he earned a reputation for wearing an enormous amount of gold and diamond jewelry, including many large necklaces with giant pendants, bracelets, huge rings on each finger, and a gold tooth.

In 1990, Slick Rick shot a bystander and his cousin whom he had hired as a bodyguard and who later admitted to having Walters shot outside a club. Slick Rick was indicted on two counts of attempted murder and pled guilty to all charges which also included, assault, use of a firearm, and criminal possession of a weapon. Russell Simmons, head of Def Jam records, bailed him out and Rick quickly recorded The Ruler's Back before spending five years in prison, two for the second degree attempted murder charges he received for that shooting, and three while hassling with Immigrations Services over his residency in the US. In the documentary film, The Show, Russell Simmons interviews Rick while he was a prisoner on Rikers Island.

"La Di Da Di", "Mona Lisa" and "Children's Story" are among his best known songs, with "La Di Da Di" being covered nearly word-for-word by Snoop Dogg on his 1993 album Doggystyle, and lines from "La Di Da Di" being borrowed by multiple high profile artists. "Children's Story" was sampled by Montell Jordan for his 1995 hit, "This Is How We Do It", and Everlast covered it for his album Eat at Whitey's. Eminem also borrowed from the song extensively in his diss song "Can-I-Bitch". "Children's Story" was also covered with similar lyrics by the MC duo Black Star on their 1998 album, Mos Def and Talib Kweli are Black Star, as well as by Tricky on the album Nearly God, with the same name and lyrics, Rapper The Game also did a similar song which was named "Compton Story" he puts on a voice like Slick Rick's throughout the track and tells a story, this rap was on the Mixtape BWS Radio 5 made in 2008.

A third album Behind Bars was recorded while still in prison, and it was released to lukewarm sales and reviews. Released from prison in 1998, he remained with Def Jam and on May 25, 1999 released a fourth album, entitled The Art of Storytelling, generally considered the authentic follow up to his 1988 debut. Storytelling was also an artistically successful comeback that paired him with MCs like Nas, OutKast, Raekwon, and Snoop Dogg, among others.

On October 6, 2008, Rick was honored on the VH1 Hip Hop Honors show.