Pomeranz was initially drafted by the Texas Rangers in 2007 but decided to go to college instead. He was then drafted by the Cleveland Indians in the first round of the 2010 Major League Baseball Draft. He signed with the Indians on August 16, 2010, right before the deadline; his contract, which included a $2.65 million signing bonus, was the largest bonus given to a college pitcher in the draft that year.
He was considered one of the top 50 prospects in baseball in 2011.
On July 31, 2011 Pomeranz, along with Alex White, Joe Gardner and Matt McBride, were traded to the Colorado Rockies for Ubaldo Jiménez. He made his Major League debut when he started and pitched five scoreless innings to pick up the win against the Cincinnati Reds on September 11, 2011. He made 4 starts in September 2011, finishing 1-2 with a 5.40 ERA.
On May 7, 2012, Pomeranz hit his first career home run.