He played 12 seasons in Major League Baseball (MLB) for the Arizona Diamondbacks, Oakland Athletics, Boston Red Sox, New York Yankees and Washington Nationals.

While coming to an agreement on his rookie contract, Drew briefly played for the Camden Riversharks of the Atlantic League, where he hit .427 in 19 games.

[2] He began the 2006 season with the Lancaster JetHawks of the Class A-Advanced California League, where he batted .389 and hit 10 home runs.

On July 13, 2006, during a game against the Milwaukee Brewers, Craig Counsell injured his ribs, prompting the call-up of Drew from the Diamondbacks' Triple-A affiliate, the Tucson Sidewinders.

In 2007, although the Diamondbacks were division champions, Drew had a disappointing season, hitting only .238 with 12 home runs but a career-high 9 stolen bases.

[3] Batting leadoff, Drew singled in the first inning, tripled in the third and homered in the fifth against Cardinal starter Joel Piñeiro.

In 2009, he hit .261 with 12 home runs and a career-high 12 triples, tied with Michael Bourn for the second most in the National League that year.

On Opening Day, April 5, 2010, he hit an inside-the-park home run against starter Jon Garland, the sixth Diamondback to do so.

On December 17, 2012, Drew signed a one-year, $9.5 million contract with the Boston Red Sox, which also included $500,000 in performance bonuses.

Under the terms of the CBA, teams signing free agents who had declined a qualifying offer would forfeit their top unprotected pick in the following draft.

[11] In 39 games he played in for the Red Sox that year, Drew hit 4 home runs, 11 RBI, and had a low batting average of just .176.

Drew became a free agent after the 2014 season, and re-signed with the Yankees on January 6, 2015, agreeing to a one-year, $5 million contract.

[24] Drew and Washington Nationals teammate Chris Heisey established a close friendship during the 2016 season, becoming the de facto leaders of a group of bench players they dubbed the "Wolfpack".