His fame began as an Internet phenomenon, rising when he released home webcam recordings of freestyle rhyming, and silly videos, and short films on the Internet previously credited to angrynakedpat.com, which aren't hosted there any more. Some of these include "Crispy New Freestyle" and "The Super Bowl is Gay."

Andy Milonakis has been compared to the Star Wars Kid and has since built a following, including comedian Jimmy Kimmel, who recruited him for regular appearances on Jimmy Kimmel Live. Milonakis was also featured in a 2005 film, Waiting... He has been a frequent co-host on the syndicated radio show Loveline with Dr. Drew Pinsky.

Milonakis has a congenital growth-hormone condition that gives him the outward appearance and voice of a pre-adolescent boy, when he is in fact a grown man. Early in life he was subjected to frequent prejudice in reference to his disorder, but he has strong hopes for biology to provide a cure. Contrary to popular belief, Milonakis was not the Man Show Boy, a smart-mouthed boy who frequently appeared on The Man Show.

In 2005 he recorded a hip hop song "Like Dis" together with his friend, J-Kwon. He is also friends with Jason Mewes, who is best known as the foul-mouthed stoner "Jay" of Jay and Silent Bob fame.