On July 31, 2009, Reddick was called up to replace Adam LaRoche, who had been traded. He made his major league debut that night, pinch-hitting for Rocco Baldelli in the ninth inning and grounding out against Cla Meredith of the Baltimore Orioles in his only at-bat. He recorded his first MLB hit in the next game, a double in the second inning off of David Hernandez. He doubled again later in the game against Chris Ray for his first multi-hit major league game.
He 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. He 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, he hit his first MLB walk-off hit against the New York Yankees, driving in Darnell McDonald in the bottom of the 10th inning.
On December 28, 2011, Reddick and two minor leaguers were traded by the Red Sox to the Oakland Athletics for Andrew Bailey and Ryan Sweeney.  Oakland general manager Billy Beane has made a habit of trading closers for talented position players as a part of the Moneyball scheme, and was able to flip Bailey, a closer, and Sweeney, who figured to be an extra outfielder for Boston, for a very good young player in Reddick. Reddick played very well for the Oakland A's and impressed Billy Beane. Reddick finished 2012 with 32 home runs (HR) and 85 RBIs, both career highs, as he helped lead the A's to the American League Division Series. He was named the American League right field Gold Glove Award winner on October 30, 2012.
Reddick in 2014
Reddick began the year as the starting right fielder. On May 7, he was placed on the disabled list with a sprained right wrist, and was activated on May 31. Through most of the 2013 season, Reddick failed to retain the power he had from the previous season. Through August 8, he had hit .203 with only five home runs on the season. But on August 9, 2013, Reddick hit 3 home runs in a single game for the first time in his career in a 14-6 rout against the Toronto Blue Jays. On the next day, he homered twice more against Toronto. The total of five home runs in two games tied the Major League record for most home runs in consecutive games. On August 26 Reddick was placed on the 15-day disabled list with an injured right wrist. He returned on September 11. From August 9 to the end of the season, Reddick hit .284/.357/.514 with 7 HR and 19 RBI. In 114 total games, he hit .226/.307/.379 with 12 HR and 56 RBI.
After the season, Reddick underwent arthroscopic surgery on his wrist, which caused him to miss 37 games on the disabled list. Reddick arrived at spring training fully healthy in 2014. On February 15, 2014 Reddick and the Athletics agreed upon a one-year $2.7 million deal, avoiding arbitration.