The left-hander will start for the Red Sox in Game 1 of the Divisional Series against the Angels in Anaheim. Lester also won the award in July.
Other pitchers considered for the honor were Zack Greinke and Joakim Soria of the Royals, Angels closer Francisco Rodriguez and Toronto's A.J. Burnett.
"He's stepped up and been a huge part of our staff. It's exciting," manager Terry Francona said after naming Lester his starter to open the playoffs. "You'll take good pitching anywhere you can get it. But when it's homegrown and you get to see him grow up right in front of your eyes, it certainly makes you proud as an organization."
In five September starts, Lester went 4-1 with a 2.14 ERA and 28 strikeouts while allowing eight earned runs on 26 hits and 13 walks in 33 2/3 innings.
Lester, who attended Bellarmine Prep High School in Puyallup, Wash, held eventual AL East champion Tampa Bay scoreless over 7 2/3 innings on Sept. 8 while tying his season-high of nine strikeouts. He then limited the Blue Jays to a run over eight innings on Sept. 14. Lester finished the regular season with six innings of one-run ball in a victory over the Indians.
"We have three or four guys who could be an ace, and I think there's a lot of guys who overlook him because we've got [Daisuke Matsuzaka] and [Josh] Beckett," Red Sox outfielder Jason Bay said. "From my point of being here, I think he's been one of our best and most consistent pitchers. And that's all you could ask, especially coming from a young guy."
The 24-year-old was 16-6 with a 3.21 ERA in 33 starts this season with 152 strikeouts in a career-high 210 1/3 innings. Lester also tossed a pair of complete-game shutouts, one of which was a no-hitter at Fenway Park on May 19 against the Royals.
Lester was pitcher of the month July, when he posted a 3-0 record and a 2.05 ERA.
Heading into the final string of games, one remaining issue Francona had to settle was his Game 1 starter, but the point became moot when Beckett suffered a right oblique strain.
"It feels good," said Lester, who was diagnosed with cancer in August, 2006. "Early on, I struggled a little bit in April and the beginning of May. I hit a good streak there for a couple of months. I really felt comfortable with myself as a pitcher, mechanically and confidence-wise. I felt like I kept building."
Lester will receive a specially designed trophy for his achievement.
Mike Scarr is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.