Spears was a regular on Fox's sketch comedy series Mad TV (1997–2005), appearing in 198 episodes, making him the second longest-serving cast member on the show behind Michael McDonald.

Spears's other film appearances include Home of Angels (1994), The Pest (1997), Jerry Maguire in which he played Teepee, brother of Rod Tidwell (1996), Out-of-Sync (1995), and The Proud Family (2003).

During his tenure, he created characters such as comedian Belma Buttons (co-host of fictional BET show "Reality Check"), Dollar Bill Montgomery (a host of an urban parody of Politically Incorrect called "Real **********ing Talk with Dollar Bill Montgomery"), James Brown Jr. (co-host of Cabana Chat), and controversial rapper Emcee Esher.

He is well known for his impressions of celebrities, including Jay-Z, Kanye West, LL Cool J, DMX, Snoop Dogg, Mike Tyson, R Kelly, Denzel Washington, Eddie Murphy and Paul Mooney.

Spears appeared in a second-season episode of Mind of Mencia, which parodied Jamie Foxx's role in Kanye West's music video for "Gold Digger."

[citation needed] According to Deadline Hollywood, Spears was expected to appear in the dark comedy feature film directed by Vladislav Kozlov The Immortalist in 2020, along with Franco Nero, Sherilyn Fenn, Paul Rodriguez, and Jeff DuJardin.