Snipes made his film debut in Wildcats starring Goldie Hawn in 1986. After Spike Lee spotted him in the Michael Jackson video Bad, the director cast him in Mo' Better Blues opposite Denzel Washington in 1990. The following year, Snipes not only took the leading role in Lee's Jungle Fever, but also portrayed one of his most memorable characters to date, that of stylish crime lord Nino Brown in Mario Van Peebles' New Jack City.

Throughout the 1990s, Snipes remained one of the biggest actors in Hollywood thanks to subsequent turns in such successful films as the emotionally wrought The Waterdance, the big-budget action flick Passenger 57 and the comedy White Men Can't Jump. Though audiences might best remember him in such action adventures as 1993's Rising Sun and 1988's Blade, Snipes has made a concerted effort to explore other directions with such films as Waiting to Exhale in 1995, To Wong Foo, Thanks for Everything! Julie Newmar (where he played an over-the-top drag queen) and One Night Stand in 1997, for which he won a Best Actor award at the Venice Film Festival.

Snipes has two children, Jelani Asar and Iset. He and his wife, April, divorced in 1990, and he has recently been coupled with painter Nikki Park.