He played in Major League Baseball (MLB) for the Kansas City Royals, Chicago Cubs, Texas Rangers, and Philadelphia Phillies.

Blanco had surgery on September 29, 2006, to repair a posterior labrum tear in his left shoulder, which he injured during a swing five days prior against the Tigers.

He later scored the winning run for the Cubs on a wild pitch thrown by Indians' closer Kerry Wood.

Blanco hit his first major league home run on July 29, 2009 while playing the Houston Astros at Wrigley Field.

[4] The Phillies re-signed Blanco to a minor league contract that included a spring training invitation on November 21, 2013.

[6] On June 7, 2017, Blanco pitched 1⁄3 of an inning in a blowout loss to the Atlanta Braves, giving up a two-run home run for an ERA of 27.00.

[11] On December 7, 2018, Blanco signed a minor league contract with the Atlanta Braves that included an invitation to spring training.