DeSena is best known for his work on the sketch comedy series All That, having joined the show's cast at the start of its seventh season in 2001 (he tied with Logan Lerman for the 2005 Young Artist Award for Best Performance in a TV Series (Comedy or Drama) - Leading Young Actor for All That). His family moved to Irvine, California in 1999 and he attended school there. He was an active member of the international ComedySportz troupe (a comic improvisation team that participates in games as seen on Whose Line is it Anyway?). More recently DeSena had been working on the online mockumentary web series Dorm Life which is a 2008 Webby Honoree for Best Writing and Comedy: Individual Short or Episode.
DeSena also has writing credit for all forty-six episodes of Dorm Life.
It is stated in a Nickelodeon Magazine Presents: Avatar issue that the creators originally intended Sokka to be much more low-key, but when DeSena came in and brought liveliness to his character, they began to give him more ad libbed and humorous parts.