After various roles in a number of productions, Adler was cast in a minor recurring role in the Fox television series Glee as school jock and bully Dave Karofsky. Glee creator Ryan Murphy was impressed with his acting and wanted to write more with him. In the November 2010 episode "Never Been Kissed", written to tackle the issue of LGBT youth bullying, Karofsky is revealed to be a closeted gay teen. Adler had previously questioned his character's motivations, but was surprised by the scene in which Karofsky kisses the object of his bullying, openly gay student Kurt Hummel (Chris Colfer). He received a positive response via the social networking websites Twitter, Tumbler, and Facebook, and commented that he was "glad to represent such a large group of people". He expanded on this, saying, "I've gotten so many messages from people all around the world these last couple of days thanking me because either they are Karofsky, they were Karofsky or they know a Karofsky." The character eventually gives up his bullying and makes his peace with Kurt, but he remains closeted. Adler has been praised for his performance in episode 3x14, "On My Way", during which, after his character is outed, he attempts suicide.
Adler is a resident artist with The Porters of Hellsgate theatre company in Los Angeles, appearing in three Shakespearean productions with them since 2008.
In October 2013 it was announced that Adler will star as Tank, Bay's college friend on Switched at Birth.