Sabathia, 39, received a standing ovation from the crowd when he departed from the 3-2 loss Wednesday in New York City. It could also have been Sabathia's last start overall for the Yankees, after the veteran pitcher announced his retirement in February. His role remains unclear for the postseason.
Sabathia allowed five hits and two runs in 2.2 innings. He allowed RBI singles to Albert Pujols and Kevan Smith before being pulled in the third inning for Domingo German.
"We hate to lose," Yankees manager Aaron Boone told reporters. "Credit to their pitchers: They executed well, and we didn't get much going, frankly. The second half of the game, our pitchers did a pretty good job of holding them down, but we couldn't mount enough."
The Yankees needed to win or for the Tampa Bay Rays to lose in order to clinch the American League East Wednesday, but neither result occurred.
Aaron Judge tied the game for the Yankees with a two-run homer in the bottom of the third frame. The Angels pulled ahead for good when Pujols reached on a fielder's choice in the sixth inning. Yankees reliever Adam Ottavino committed a throwing error on the play, allowing Michale Hermosillo to score the go-ahead run.
Yankees outfielder Giancarlo Stanton went 1 for 3 in his return from the injured list. Stanton hadn't played since June 25. Angels second baseman David Fletcher went 3 for 5. Pujols and Smith went 2 for 5 with an RBI in the win.
"Walking off was cool," Sabathia said. "Seeing my mom. Seeing my wife. My kids were happy. It was pretty cool."
The Yankees host the Angels in the final game of the series at 6:35 p.m. EDT Thursday at Yankee Stadium.