On July 31, 2009, Reddick was called up to replace the traded Adam LaRoche on the roster. Reddick made his major league debut that night, pinch hitting for Rocco Baldelli in the ninth inning. Reddick grounded out against Cla Meredith of the Baltimore Orioles in his only at-bat. He recorded his first major league hit in the next game, a double in the second inning, on his first at-bat off David Hernandez. Reddick doubled again later in the game against Chris Ray for his first multi-hit game.
On August 2, 2009, Reddick recorded his first major league home run against Brian Bass. He was the first Red Sox outfielder to hit a home run within his first three games since Billy Conigliaro in 1969.
Reddick was optioned back to the Triple A-Pawtucket Red Sox on August 5. The move allowed a depleted Red Sox bullpen to use Billy Traber's services. He was recalled the very next day, when Rocco Baldelli was placed on the disabled list with a left ankle contusion.
Reddick started 2010 in Pawtucket, but was recalled in April 2010 after Mike Cameron went on the DL.
Reddick again started 2011 in Pawtucket, but was recalled in May 26, 2011 after Darnell McDonald was placed on the 15-day disabled list with a strained left quad. Reddick was able to stay in the majors after the Red Sox designated Cameron for assignment on June 29, 2011, effectively removing Cameron from the active and 40-man rosters, leaving room for Reddick.
On August 7, 2011, Reddick hit his first MLB walkoff hit against the New York Yankees driving in Darnell McDonald in the bottom of the 10th