Key is perhaps best known as one-half of the comedy duo Key & Peele with Jordan Peele, whom he met while starring on the FOX late-night sketch comedy series Mad TV. Their own sketch series, also titled Key & Peele, ran on Comedy Central from 2012 to 2015. In 2016, Key and Peele starred in the comedy film Keanu, which they also produced.
He is also the biological half-brother of late comic book writer Dwayne McDuffie, with whom he shared a father. Neither Key nor McDuffie were aware of the other's existence in the latter's lifetime, and the former only learned of their relationship after his death.
- Mad TV (2004 — 2009) as himself / various characters
- Reno 911! (2005 — 2008) as Hypothetical Criminal
- Role Models (2008) as Duane
- Childrens Hospital (2010 — 2015) as Cop / Captain Tripper
- Just Go With It (2011) as Ernesto
- Key & Peele (2012 — 2015) as himself / various characters note
- Afternoon Delight (2013) as Bo
- Whose Line Is It Anyway? (2013 — 2016) as himself
- The LEGO Movie (2014) as Frank the Foreman (voice)
- Fargo (2014) as FBI Special Agent Bill Budge
- Parks and Recreation (2014 — 2015) as Joe
- Horrible Bosses 2 (2014) as Mike
- HUNT the TRUTH (2015) as Benjamin Giraud
- Super Mansion (2015 — present) as American Ranger
- Pitch Perfect 2 (2015) as Beca's Boss
- Tomorrowland (2015) as Hugo Gernsback
- Vacation (2015) as Jack Peterson
- Hotel Transylvania 2 (2015) as Murray the Mummy (voice)
- Keanu (2016) as Clarence / Smoke Dresden note
- The Angry Birds Movie (2016) as Judge Peckinpah (voice)
- Storks (2016) as Alpha Wolf (voice)
- Why Him? (2016) as Gustav
- Friends from College (2017 — present) as Ethan Turner
- Samurai Jack (2017) as Da Samurai (voice, taking over from David Alan Grier)
- The Predator (2018) as TBA
Keegan Michael-Key provides examples of the following tropes:
- Bald of Awesome
- But Not Too Black: Born to a black father and white mother, and his own chiseled features make this even harder to pin down.
- Keet: Displays a surprising amount of energy for his age, most notably with all his jumping and kicking as Luther. And despite being left to sit out the musical numbers on Whose Line, he's incapable of sitting still.
- Large Ham: And massively so.
- Those Two Guys: With Jordan Peele.