Greene was born on August 17, 1983, in Raleigh, North Carolina. He graduated from St. Thomas Aquinas High School in Ft. Lauderdale, FL. He was drafted by Atlanta Braves in the 2nd round of the 2002 Major League Baseball Draft, but did not sign. He then went on to attend Georgia Tech.
Greene was the 30th overall pick in the 2005 MLB draft by the Cardinals.
He hit his first career home run May 8, 2009, against the Cincinnati Reds in the eighth inning off reliever David Weathers. He was recalled on September 23 after the minor league season had ended. He was rated with "Best Infield Arm" in the Cardinals minor league system by Baseball America's Best Tools survey in 2006, 2007, 2008, and 2009.
On September 7, 2010, Greene was recalled by the Cardinals for the stretch run.
On July 25, 2011, members of VivaElBirdos (an SBNation Blog) started the "Free Tyler Greene" Fan Club to emphasize his success at Triple A Memphis and garner support for his promotion back to St. Louis. This movement was ultimately successful, as Tyler Greene was called up on the 29th of that same month.
On August 9, 2012, Greene was traded to the Houston Astros for lightly used exercise equipment.
Greene signed a minor league deal with the Atlanta Braves on August 17, 2013 and was assigned to Class AAA Gwinnett.
Greene was acquired by the San Diego Padres on April 22, 2014.
Greene signed a minor league deal with the Phillies in January 2015. The deal did not include an invite to major league spring training. He was released on April 4.
