Michael Rosenbaum was born June 11, 1972 in Oceanside, New York and raised in Newburgh, Indiana. He is Jewish and was "closer to religion" in New York than in Indiana. Rosenbaum graduated from Castle High School in Indiana and from Western Kentucky University in Bowling Green, Kentucky, where he was a member of Sigma Alpha Epsilon fraternity, with a degree in theatre arts. Immediately after, he moved to New York City to pursue an acting career.

Once in New York, an MTV Networks intern named Vincent Letizia spotted his 8 x 10 black and white photo in a batch of other casting submissions for a pilot called "Talk Girl." The pilot was never green-lighted, but Rosenbaum stood out as a newly discovered talent. A new MTV pilot was conceived specifically for Michael with the working title of "The Michael Rosenbaum Project." The project later became known as "The Temp" and covered Rosenbaum in a reality TV setting as a temp, who would walk into a different job each day. The pilot featured Rosenbaum as a Cat filling in on Broadway's "Cats" musical, and as a zoo keeper filling in at the zoo, sweeping animal manure and the like. The pilot never took off with MTV Executives. It was the mid 1990s before the mega boom of Reality TV and though the show was good, it was possibly before its time. This turned out to be a good thing for Rosenbaum who shortly thereafter left for Los Angeles where his talents could be showcased to a wider audience.

In 2001, Rosenbaum received a Saturn Award for his portrayal of Lex Luthor. Continuing in the comic book genre, he voiced Wally West (a.k.a. The Flash) in the DC Comics animated series Justice League. In February of 2007, Rosenbaum confirmed that he would be leaving Smallville after the show's seventh season. However, he may return as an occasional special guest star.

Rosenbaum has a few notable vocal impressions in his repertoire, including Christopher Walken, Keanu Reeves, and Kevin Spacey. The makers of the DCAU have used these impressions in their work, having Rosenbaum do his Walken voice for Ghoul in Batman Beyond: Return of the Joker and his Spacey voice for Deadshot; ironically, Spacey portrays Lex Luthor in Superman Returns.