Worthington retired for a second time after the 1968 season, but in May 1969, Twins' manager Billy Martin convinced him to come back. "It took me a while to get back in shape," Worthington said, but he made scoreless appearances in his first three games, starting June 8. He allowed a run on June 14, though, then saw his ERA shoot up to 17.18 as he gave up six runs in in an inning on June 17, in a 13–1 loss to the Angels. Over his next 25 games through August 7, he had a 2.20 ERA before posting a 7.71 ERA in his final 16 games. In the first game of a doubleheader against the White Sox on July 16, he allowed one run in four innings and earned the win as the Twins prevailed by a score of 9–8. On July 25, he relieved Jim Perry with two outs and a runner on third in the seventh inning of a game against the Indians, striking out Chuck Hinton to keep the score 2–0. Tasked with finishing the game, he blew the lead in the ninth when Duke Sims hit a tying two-run home run against him. However, he threw a scoreless 10th and 11th innings, and the Twins ultimately prevailed 4–2 in 16 innings. In 46 games, Worthington had a 4–1 record, though his 4.57 ERA was his highest since 1960 and he only had three saves. He struck out 51 batters and walked 20, giving up 65 hits in 61 innings. The Twins won the newly created AL West division title and faced the Orioles in the inaugural AL Championship Series. Worthington relieved Tom Hall with the Twins trailing 5–1 and pitched a scoreless fifth inning. However, after retiring Jim Palmer to start the sixth, he allowed three straight hits, including an RBI single to Frank Robinson, before he was replaced on the mound by Joe Grzenda. It was his last major league appearance, as the Orioles swept the Twins in three games.