In June 2000, J.B. Smoove landed his first big feature film role narrating and starring in "Pootie Tang" with actor/comedian Chris Rock. In March 2001, Smoove landed another pivotal role in the comedy film "Say Uncle" starring Tom Green. This year, he paired up with Adam Sandler to co-star in "Mr. Deeds." The collaboration between the two was so successful that Smoove signed a writing deal with both Revolution Studios and Happy Madison (Sandler's production company).

Smoove has appeared on the comedy shows "Uptown Comedy Club," "Russell Simmons Def Comedy Jam," "Comic View" and "It's Showtime at the Apollo."

He had a recurring role on "The Lyricist Lounge Show," as well as featured guest spots on "The Chris Rock Show" and "Premium Blend." Soon after, Smoove was cast in such films as "Lesser Prophets" starring Jimmy Smits and Scott Glenn, and "Tomorrow Night," featuring Conan OBrien.