After surrendering a two-out RBI single to Maicer Izturis and a two-run triple to Erick Aybar, Beckett was replaced with his team trailing by three runs.
Red Sox manager Terry Francona relieved his big-game right-hander with lefty Billy Wagner, who stranded Aybar at third by striking out Chone Figgins.
Yet the damage was done as the Angels claimed a 4-1 victory to grab a 2-0 advantage in the best-of-five American League Division Series.
"This one is mine," Beckett said, accepting responsibility for the loss. "It [stinks]. If I make one of those two pitches, maybe they don't have to score three runs. They score one."
In command through six innings, Beckett and Angels right-hander Jered Weaver were locked in a 1-1 tie.
Momentum shifted in the seventh, as Beckett lost command of his offspeed pitches.
"I made a [terrible] pitch to Izturis. I made a [terrible] pitch to Aybar," Beckett said. "When you have poor location, you get your [butt] kicked."
Once the damage was done, Francona went to the bullpen.
"Tito has to manage the game," Beckett said.
Already established as one of the top big-game pitchers of his era, Beckett saw his playoff record fall to 7-3. The last time he lost in the postseason was in Game 3 of the 2003 World Series, when he was with the Marlins.
Since that game against the Yankees, Beckett was 6-0 with a 3.04 ERA in eight postseason starts.
Entering the seventh inning on Friday, Beckett hadn't walked a batter, and the right-hander was economical with his pitches -- compiling 75 total.
With Vladimir Guerrero leading off the seventh inning, Beckett went after the slugger with a dose of breaking balls.
Beckett started the sequence with three consecutive offspeed pitches, with none finding the strike zone. After taking a fastball for a strike, Guerrero drew the only walk the Boston starter allowed on the night.
"It's Vlady up there. My approach hasn't changed much in the last six or seven years facing him," Beckett said. "I'm definitely trying not to leave a breaking ball up over the plate there."
Beckett also fell behind 3-0 in the count to Kendry Morales, who eventually lifted a fly ball to left field for the first out. On a night Beckett was throwing strikes, signs of trouble came when he faced successive 3-0 counts to open the inning.
"I would never take him out after a 3-0 count," Francona said. "He's thrown a three- or four-hitter going into that inning. No, I didn't think he was tired. I thought he was fine."
Howard Kendrick pinch-ran for Guerrero, and with one out he stole second. Mike Lowell at third base made a nice stop on Juan Rivera's hard ground ball to third for the second out.
Despite having a runner on second base, Beckett was in position to close out the inning with the score knotted at 1. But Izturis singled to center on a breaking ball that was up.
The frustrations of the inning mounted when Mike Napoli was hit by a 2-1 breaking ball. The ball plunked Napoli on the back. Immediately, Beckett contended to home-plate umpire CB Bucknor that Napoli didn't make an attempt to get out of the way. Francona came out of the dugout to make a similar case.
During the exchange, Beckett was upset that Bucknor wouldn't listen to his plea.
"I wasn't much [ticked] that he wouldn't overturn the pitches, but show me a little bit of respect," Beckett said. "He just straight-faced me and then walked away. I was just like, I went up to [catcher Victor Martinez]. I said, 'Vic, he'd be [ticked] if I did that to him.' I'm not asking him to even overturn it, just listen to what I have to say. Don't like, take your mask off, straight-face me and then walk away. I can't say anything to the point of getting thrown out."
Beckett added the hit by pitch didn't carry over to his approach to Aybar, who padded the Angels' lead with his two-run triple.
But after that triple, Beckett's night was over after 103 pitches.
Now down two games, the Red Sox are in need of three consecutive victories to advance. If a fifth game is forced, Beckett would be back on the mound.
"I thought he pitched pretty good," Red Sox shortstop Alex Gonzalez said. "He was very good tonight, but he had that bad inning. It's a five-game series, maybe he can come back here and have another chance."