The Rays defeated the Red Sox in the ALCS, and went on to lose the 2008 World Series to the National League champion Philadelphia Phillies.

In a re-match of last year's ALDS, starters Jon Lester and John Lackey were sharp early on, each tossing a couple of scoreless innings.

The game entered the ninth inning tied at five but that deadlock was broken after a double by David Ortiz and a two-run home run to center by J. D. Drew off Angels closer Francisco Rodríguez.

A fielding miscue by the Angels in the second inning caused a fly ball hit by Jacoby Ellsbury to drop between Torii Hunter and Howie Kendrick in shallow center field, scoring three runs (Jed Lowrie, Jason Varitek, and Coco Crisp) and giving the Red Sox a two-run lead.

The next inning, Mike Napoli tied the score with a two-run home run over the Green Monster that completely left the ballpark.

In the eighth inning, a passed ball allowed Mark Teixeira and Vladimir Guerrero to advance on second and third, and they subsequently scored on a single by Torii Hunter to tie the game.

In the top of the ninth inning, the Angels threatened with a leadoff double by pinch hitter Kendry Morales followed by a sacrifice bunt, but when Erick Aybar failed to make contact on a suicide squeeze attempt, the runner was tagged out.

In the bottom of the ninth inning, Jed Lowrie won the game with a walk-off single, scoring Jason Bay from second base.

2008 ALDS (3–1): Boston Red Sox over Los Angeles Angels of Anaheim The Rays went up 1–0 in the second on rookie Evan Longoria's leadoff home run in his first postseason at-bat off Javier Vazquez, but starter James Shields allowed consecutive leadoff singles in the third before DeWayne Wise's two-out three-run home run put the White Sox up 3−1.

After B. J. Upton struck out, Willy Aybar's sacrifice fly tied the game before Longoria's home run put Tampa up 4–3.

They added insurance in the eighth when B. J. Upton hit a leadoff triple and scored on Carl Crawford's single to knock Buehrle out of the game.

In the sixth inning, the White Sox added an insurance run when Juan Uribe drove in Brian Anderson with two outs.