The regular season ended with a record of 94–68 and the Angels winning the American League West title for the sixth time.

However, the Angels' playoff run quickly ended, as they were swept by the Boston Red Sox in the American League Division Series, just as they were in 2004.

In November, they signed former Texas Rangers center fielder Gary Matthews, Jr. to a 5-year contract worth $50 million.

The Angels of Anaheim solidified their bullpen for the 2007 season by re-signing set-up man Scot Shields and closer Francisco Rodríguez each to one-year contracts and acquiring Justin Speier and Darren Oliver via free agency.

Late in spring training, third baseman Chone Figgins fractured his finger, putting him out of action for the first month of the season.

With a solid record of 5–2 and first place in the division after the first week of the season, the Angels of Anaheim traveled onto the road to take on the Indians.

During the game against the Athletics on April 18, second baseman Howie Kendrick was hit by a pitch, and placed on the 15-day disabled list.

The Angels of Anaheim won the series opener to extend their winning streak to a season-high six games, in which they outscored their opponents 37–10.

The Angels of Anaheim ended the month by taking two of three against the Mariners and losing the first game of a four-game series with the Orioles.

Jered Weaver won his 5th consecutive decision in a costly effort; Weaver jammed his shoulder sliding into 2nd base, Garret Anderson injured his right hip and was placed on the 15-day disabled list after the game, and Casey Kotchman suffered a concussion when a pickoff throw hit him in the helmet.

Gary Matthews, Jr. hit his first career inside-the-park home run and the Angels won the final game 10–4.

The Angels trailed 9–4 going into the bottom of the 7th inning, where they scored 5 runs, capped off by Figgins' 5th hit of the night, an infield single.

Astros pitching walked 4 consecutive Angels batters, tying up the score, before Vladimir Guerrero hit a three-run home run.

The Angels blew a late-inning lead when Xavier Nady hit an RBI-single off Francisco Rodríguez to tie the game 3–3.

However, in the 10th inning Erick Aybar hit the Angels second walk-off ground-rule double in the series to win the game 4–3.

In the series opener, the Angels blew a 5-run lead, an Oriole rally highlighted by Aubrey Huff hitting for the cycle.

The Angels, hoping to end the first half with a successful week, continued their road trip in Texas.

The Angels split the final two games of the series, and concluded their road trip, and the first half of the season, by taking on the New York Yankees.

Guerrero won the Home Run Derby, and Rodriguez earned the save in the American League's 5–4 victory.