Lee won his third straight start since joining the Philadelphia Phillies.
The win clinched the Phils first sweep at Wrigley Field in 25 years.
Ryan Howard and Pedro Feliz homered in the fourth inning to put the Phillies up for good. Howard later stole a base and scored on a Feliz single.
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Shane Victorino had two hits and scored twice. The All-Star center fielder had no problems with the crowd, a day after he was doused with beer while trying to catch a fly ball, prompting Victorino (and the Cubs) to file a police report.
Ryan Dempster (6-6) gave up all six runs for the reeling Cubbies.
Next up for the Phillies is a battle in Atlanta against the second-place Braves.