On July 31, 2008, Bay and a player to be named later (Josh Wilson) were traded to the Boston Red Sox in a three team deal that sent Manny Ramirez to the Los Angeles Dodgers and Andy LaRoche with Bryan Morris to the Pittsburgh Pirates from the Dodgers and Brandon Moss with Craig Hansen to the Pirates from the Red Sox. In his Red Sox debut, Bay scored both runs, the second coming after he hit a triple in bottom of the 12th inning and scored the game winning run on a Jed Lowrie RBI infield single. Bay hit his first home run with Boston the next night against Oakland. In one game, he hit multiple home runs against the Baltimore Orioles at Oriole Park. He would end the 2008 season with Boston batting .293 with 9 home runs and 37 RBI.

The Sox' 2008 American League Division Series against the Los Angeles Angels of Anaheim was the first playoff series of Bay's career. Bay hit a home run in each of the first two games of the series. Bay finished the series batting 7 for 17 (.412), with 2 doubles, 2 home runs, and 5 RBIs. In the 2008 American League Championship Series he scored the first run in game one. In game two he opened the door for the Red Sox with a two-run double and a home run in the fifth inning. However the Boston Red Sox lost in seven games.

2009 - After a clutch first half start, including an All Star selection, Bay went on to lead the Red Sox with a career high 36 home runs and 119 RBIs during the regular season. Early in the season he had a streak of 11 home runs with men on base, tying the team record and falling one shy of the major league mark.

In 2009, he was named # 41 on the Sporting News' list of the 50 greatest current players in baseball.

He filed for free agency after the season, turning down the Red Sox's offer of salary arbitration