| Year | Title | Role | Notes |
| 1993 | Ordeal in the Arctic | Master Warrant Officer Tom Jardine | Television film |
| 1994–1997; 2007 | One Life to Live | Joey Buchanan | |
| 1996 | Spin City | Guy | Uncredited; Episode: "A Star Is Born" |
| 1997 | Total Security | Troy Larson | Episode: "Das Bootie" |
| 1998 | Maggie Winters | Ronald | Episode: "Mama's Got a Brand New Bag" |
| 1998–2001 | Two Guys and a Girl | Johnny Donnelly | Main role |
| 1999 | The Outer Limits | Michael Ryan | Episode: "Star Crossed" |
| 2001 | King of the Hill | Frisbee Guy | Voice; episode: "Luanne Virgin 2.0" |
| 2002 | Pasadena | Rev. Glenn Collins | 3 episodes |
| Firefly | Malcolm "Mal" Reynolds | Main role |
| 2003 | Alligator Point | Bill | Pilot |
| Buffy the Vampire Slayer | Caleb | Recurring role |
| Miss Match | Adam Logan | Recurring role |
| 2004 | Hollywood Division | Det. Tommy Garrett | Pilot |
| 2005–2006 | Justice League Unlimited | Vigilante | Voice; 3 episodes |
| 2006 | Lost | Kevin Callis | Episode: "I Do" |
| 2007 | Drive | Alex Tully | Main role |
| 2007–2014 | Robot Chicken | Flash, Roger Brown, Harry S. Stamper, Matt Trakker, Rick Berman, Lumiere, Tony Hayward, Mr. Phillipson, Bionic-1, Black Dragon, Green Lantern, Westeros Detective, Jigsaw, Various Voices | Recurring role |
| 2007–2008 | Desperate Housewives | Dr. Adam Mayfair | Recurring role |
| 2009–2016 | Castle | Richard Castle | Main role |
| 2010–2018 | The Venture Bros. | Brown Widow | Voice; 4 episodes |
| 2012 | American Dad! | Joel Larson, Liver | Voices; episode "The Kidney Stays in the Picture" |
| 2012 | American Dad | American Businessman Klaus | Voice; episode "Love, AD Style" |
| 2013 | Writers Guild of America Awards 2012 | Himself (host) | Television special |
| 2014–2015 | Community | Bob Waite | 2 episodes |
| 2014–2016 | Gravity Falls | Preston Northwest | Voice; Recurring role |
| 2015 | The Big Bang Theory | Himself | Episode: "The Comic Book Store Regeneration" |
| Kroll Show | Mountie McMinniman | Episode: "Twins" |
| Drunk History | Wernher von Braun | Episode: "Space" |
| 2016 | HarmonQuest | Tetter Spice | Episode: "Earthscar Village" |
| 2016–2018 | Modern Family | Rainer Shine | 7 episodes |
| 2017–2018 | Santa Clarita Diet | Gary West | 6 episodes |
| 2017 | Rick and Morty | Cornvelious Daniel | Voice, episode: "The Rickshank Rickdemption" |
| Brooklyn Nine-Nine | Mark Deveraux | Episode: "Serve & Protect" |
| 2017–2025 | Big Mouth | Himself, Nate | Voices; Recurring role |
| 2018 | A Series of Unfortunate Events | Jacques Snicket | Recurring role |
| The Magic School Bus Rides Again | Axle ValveStuck | Voice; episode: "Waste Not, Want Not" |
| American Housewife | Himself | 2 episodes |
| 2018–present | The Rookie | Officer John Nolan | Main role; also executive producer |
| 2021–2022 | Resident Alien | Number 42 – Octopus in tank | Voice, Recurring role |
| 2021 | M.O.D.O.K. | Wonder Man | Voice; episode: "This Man... This Makeover!" |
| 2022–2025 | The Recruit | CIA Director Alton West | Recurring role |
| 2022–2023 | The Rookie: Feds | Officer John Nolan | 3 episodes |
| 2024 | Monsters at Work | Johnny Worthington III | Voice; Recurring role |
| 2025 | Krapopolis | Zan | Voice; 2 episodes |
| Family Law | Bud Nielsen | Episode: "Second Chances" |
| The Mighty Nein | The Gentleman | Episode: "Many Gifts" |
| Peacemaker | Guy Gardner / Green Lantern | Episode: "The Ties That Grind" |
| 2026 | Lanterns † | |
