In 2005, De Aza batted .286 with 34 stolen bases and 75 runs scored while playing for the Marlins Single-A Jupiter affiliate. In 2006, De Aza batted .278 with 12 doubles, two triples, two home runs, 16 RBI and 27 stolen bases at Double-A.
On March 28, 2007, De Aza was named the starting center fielder for the Marlins, beating out Reggie Abercrombie, Eric Reed, and Alex Sánchez in what was seen as a surprise. In 2007, he batted .303 (10-for-33) in nine games for the Marlins before going on the disabled list on April 16 with a right ankle sprain; an MRI in mid-May revealed that his ankle had a hairline fracture. The fractured ankle required surgery and De Aza was placed on the injured reserve list for the 2007 season. De Aza was called up by the Florida Marlins in May 2009.
On January 18, 2013, De Aza signed a one-year, $2.075 million deal to avoid arbitration with the White Sox. De Aza was the starting center fielder once again, and his main backups were Jordan Danks and DeWayne Wise. He would also periodically fill in at left field when Dayán Viciedo would be injured. In 153 games, he hit .264/.323/.405 with 17 HR, 62 RBI and 20 SB.
On August 30, 2014, De Aza was traded from the Chicago White Sox to the Baltimore Orioles for two minor league pitchers, Miguel Chalas and Mark Blackmar.  In his first 5 games with the Orioles, De Aza hit 2 homeruns, had 3 RBI, stole a base, scored 4 runs and batted .400.