| Dec 21 | Sealab 2021Animated series | 2000–2005 | 4 | 52 | Sitcom | Adam Reed |
| Dec 30 | Aqua Teen Hunger ForceAnimated series | 2000–2015 | 12 | 139 | Comedy | Dave Willis |
| Dec 30 | Harvey Birdman, Attorney at LawAnimated series | 2000–2007 | 4 | 39 | Legal drama | Michael Ouweleen |
| — | Captain LingerWeb series | 2001 | 1 | 8 | Superhero | |
| Apr 1 | UndergradsAnimated series | 2001 | 1 | 13 | College life | |
| Feb 16 | The Venture Bros.Animated series | 2003–2018 | 7 | 81 | Comedy | Doc Hammer, Christopher McCulloch |
| Aug 1 | Stroker and HoopAnimated series | 2004–2005 | 1 | 13 | Comedy | |
| Nov 7 | Perfect Hair ForeverAnimated series | 2004–2014 | 3 | 9 | Comedy | Mike Lazzo, Matt Harrigan |
| Nov 14 | Tom Goes to the MayorAnimated series | 2004–2006 | 2 | 31 | Adult animation | Tim Heidecker |
| Feb 20 | Robot ChickenAnimated series | 2005 | 11 | 227 | Adult animation | Seth Green, Matthew Senreich |
| Jun 19 | 12 oz. MouseAnimated series | 2005–2018 | 3 | 22 | Exploitation | Matt Maiellaro |
| Oct 16 | SquidbilliesAnimated series | 2005–2016 | 13 | 110 | Comedy | Dave Willis |
| Oct 30 | Lucy, the Daughter of the DevilAnimated series | 2005–2007 | 1 | 11 | Adult animation | Loren Bouchard |
| Nov 6 | The BoondocksAnimated series | 2005–2014 | 4 | 55 | Comedy | Aaron McGruder |
| Dec 13 | Moral OrelAnimated series | 2005–2008 | 3 | 43 | Comedy | Dino Stamatopoulos |
| Mar 19 | MinoriteamAnimated series | 2006 | 1 | 19 | Adult animation | |
| Aug 6 | MetalocalypseAnimated series | 2006–2013 | 4 | 63 | Music | Tommy Blacha, Brendon Small |
| Oct 16 | Frisky DingoAnimated series | 2006–2008 | 2 | 25 | Satire | Adam Reed |
| Nov 26 | Assy McGeeAnimated series | 2006–2008 | 2 | 20 | Detective | Matt Harrigan |
| Feb 11 | Saul of the Mole Men | 2007 | 1 | 20 | Comedy | |
| Feb 11 | Tim and Eric Awesome Show, Great Job! | 2007–2010 | 5 | 50 | Sketch comedy | Tim Heidecker |
| May 13 | Superjail!Animated series | 2007–2014 | 4 | 36 | Adult animation | |
| Sep 14 | Out of Jimmy's Head | 2007 | 1 | 20 | Comedy | |
| Nov 4 | Xavier: Renegade AngelAnimated series | 2007–2009 | 2 | 20 | Adult animation | Vernon Chatman, John Lee |
| Apr 1 | Delocated | 2008–2013 | 3 | 30 | Comedy | Jon Glaser |
| Apr 1 | Fat Guy Stuck in Internet | 2008 | 1 | 10 | Science fiction | John Gemberling |
| Nov 23 | The Drinky Crow ShowAnimated series | 2008–2009 | 1 | 10 | Comedy | Tony Millionaire |
| Dec 8 | Childrens Hospital | 2008 | — | 86 | Satire | Rob Corddry |
| Apr 17 | G.I. Joe: Resolute | 2009 | 1 | 11 | — | |
| Apr 19 | The Rising Son | 2009 | 1 | 4 | — | |
| Sep 27 | Titan MaximumAnimated series | 2009 | — | 72 | — | Matthew Senreich |
| Nov 3 | InfomercialsWeb series | 2009 | 2 | 15 | Short | |