Day was born in Orange County, California. He graduated from El Modena High School in 1998, where he was involved in the drama program. Day also portrayed a victim in a staged automobile accident to give his fellow classmates a sense of the dangers of intoxicated driving.

In 2002, Mikey graduated from UCLA with a degree in theatre. Day is a graduate of the Groundlings school in Los Angeles, California. He performed at the Improv Olympics in Hollywood for three months. Day made a guest appearance on The WB's series Angel in 2004. He had appeared on MTV's reality series Faking the Video. He also appeared on an episode of the improv comedy series World Cup Comedy.

Day was a performer on MTV's improv comedy series Wild 'N Out. Day appeared in a sketch comedy series called The Underground on Showtime. He is also known for his role as Evan Ferguson in the YouTube video series David Blaine Street Magic: YouTube Edition.

Day starred in NBC's primetime comedy Kath & Kim and is dating his costar Selma Blair.

Day hosted a recurring segment called "JMZ" on The Jay Leno Show.