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The left-hander, whose rookie season was cut short when he was diagnosed with a treatable form of lymphoma, pitched six innings to lead the Red Sox to a 6-2 win over the Cleveland Indians on Monday night.
"I figured the day would come," Lester said. "I just didn't know when. It's just nice to be back."
Working to major leaguers for the first time in 11 months while his parents sat on the edges of their seats near Boston's dugout, Lester allowed two runs and five hits to easily handle the Indians, the team with the AL's best home record.
Lester's journey back couldn't have had a better checkpoint.
"It was supposed to be his night," Red Sox manager Terry Francona said.
Meanwhile, Johan Santana was having one of the worst starts of his career in Toronto.
Santana allowed a career-high four home runs, including two to Frank Thomas, and the Toronto Blue Jays beat the Minnesota Twins 6-4.
Santana (11-8) has given up three home runs five times in 162 previous starts but not since May 7, 2004, against Oakland.
"Those guys were aggressive, they were swinging right away," Santana said. "It seemed like the ball was flying today."
Santana dropped to 41-6 following the All-Star game since the 2003 break. He allowed six runs and seven hits in five innings, matching his shortest start this season.
"He was up and when you're up against big hitters, that's what happens, the ball goes out of the ballpark," Twins manager Ron Gardenhire said.
Justin Morneau hit two home runs for Minnesota.
Shaun Marcum (6-4) allowed four runs and eight hits in six innings. Casey Janssen pitched 1 2-3 perfect innings, Scott Downs got Morneau on a grounder to end the eighth and Jeremy Accardo finished for his 16th save in 19 chances.
In other AL games, it was New York 9, Kansas City 2; Detroit 9, Chicago 6; Texas 8, Seattle 7; and Oakland 12, Los Angeles 6.
In Cleveland, Lester showed the same form that made him instantly popular at Fenway Park, where he is certain to have another emotional game when he finally pitches there again.
The 23-year-old left-hander had been in the midst of a stellar first season when a visit to the doctor for back pain resulted in a startling find that threatened his life and stunned Red Sox Nation.
Lester was diagnosed with anaplastic large cell lymphoma just days after he improved to 7-2 with a win over the Los Angeles Angels on Aug. 23.
"I'm just trying to put it behind me and move on and just go back to pitching and not worry about things," he said. "But right now every three months I have to go back and get that reality check. Hopefully we can put it behind us and just win some games."
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Coco Crisp went 4-for-5 and scored three runs for Boston, which jumped to a 5-0 lead in the second off Jake Westbrook (1-6).
Manny Ramirez had two RBIs as the Red Sox became the majors' first team to reach 60 wins.
"This isn't even about baseball," Curt Schilling said. "It just doesn't get any better the way a guy like that comes back to us. It's about family. The big thing is he's a great human being and that makes it an even better story. That wasn't your run-of-the-mill DL stint."
Yankees 9, Royals 2
Roger Clemens (3-4) got his 351st career victory and Alex Rodriguez became the first player to reach 100 RBIs this season as visiting New York extended its winning streak to four.
Clemens gave up two runs and four hits in seven innings, walking none and striking out three to raise his total to 4,641, second to Nolan Ryan on the career list.
Kansas City's Odalis Perez (5-9) gave up four run, eight hits and three walks in seven innings.
Tigers 9, White Sox 6
Mike Hessman, called up from Triple-A Toledo earlier Monday, hit a go-ahead two-run single with two outs in the seventh for visiting Detroit.
Jason Grilli (4-2) pitched 1 1-3 innings of relief to earn the victory for the Tigers, who have won 12 of 16. Todd Jones pitched a perfect ninth for his 27th save.
Mark Buehrle (7-6) lasted 6 1-3 innings, but gave up a season-high seven runs and tied a career high with 14 hits allowed.
Rangers 8, Mariners 7
Sammy Sosa hit career home run No. 603 and had five RBIs for host Texas.
Sosa was 6-for-43 (.140) with one RBI over his last 12 games. He was in an 0-for-10 slump before his two-run double in the third put the Rangers ahead 3-2.
Brad Wilkerson added his 15th homer in the fifth, a two-run shot that chased Horacio Ramirez (5-3). Kevin Millwood (7-8) won despite allowing 12 runners on eight singles and four walks in 5 1-3 innings.
Athletics 12, Angels 6
Mike Piazza hit a three-run homer and an RBI double and Mark Ellis added two solo homers and an RBI double for visiting Oakland, which won for the third time in 14 games.
The A's rocked Bartolo Colon for four runs in the first inning. Colon (6-6) left after the first inning because of soreness in his right elbow.
Joe Kennedy (2-9) allowed one hit in two scoreless innings to earn his first victory in 10 career decisions against the Angels.
[Associated Press]
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