The Cubs, who outlasted the Padres in a 4-hour 48-minute, 13-inning marathon Tuesday night, won for the fifth time in 19 games and won consecutive games for the first time since a three-game streak July 29-31.
"It didn't look like he played 13 innings last night," San Diego manager Bruce Bochy said of Sosa. "He's resilient. He looked like it was opening day."
Sosa led off the fourth inning against Brian Tollberg with his first homer since Aug. 21 to break a 1-1 tie. With two outs and two on in the fifth, Sosa hit a 3-1 pitch from Tollberg into the left center field bleachers to go ahead 5-1.
It was Sosa's fifth two-homer game this season and 44th of his career. In his last 16 games, Sosa has nine homers and 17 RBIs. He is on pace to finish with 55 homers.
"I'm not the type of person who looks at the stats," Sosa said. "I just want to be ready every day. If I do that, the numbers will be there."
With one on and two outs in the seventh, Tollberg intentionally walked Sosa, who finished 3-for-3 with a single in the first.
"He's leading the league in home runs for a reason," Tollberg said.
Jon Lieber (12-7) gave up one run and four hits in eight innings to set his career high in wins, set in 1997. He struck out seven and raised his career-high innings total to 209 2-3.
Cubs manager Don Baylor talked to Liebeabout going the distance but pulled him after 112 pitches.
"A complete game was not the most important thing for me," said Baylor, who doesn't want to overuse Lieber and plans to give him extra rest the remainder of the season.
"He pitched great and hit his spots but we didn't," San Diego's Ryan Klesko said. "When you make mistakes to big hitters, it's tough. Sosa made us pay both times."
Tollberg (3-3) gave up five runs and 10 hits in eight innings, striking out four, as the Padres lost for only the fourth time in the last 11 games.
Damian Jackson tripled with one out in the Padres' first and scored on Klesko's double.
The Cubs answered in the first with Mark Grace's two-out, RBI double, scoring Sosa who had singled.
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