Randy Wells (3-3) picked up his third straight victory by limiting the Pirates to a run on six hits over seven innings. Kevin Gregg worked a 1-2-3 ninth for his 14th save.
Sam Fuld opened the Chicago first with a double off Virgil Vasquez and moved to third on a sacrifice by Ryan Theriot. Lee followed with his 12th homer.
Pittsburgh scored its only run in the bottom of the first on an RBI single by Brandon Moss, but the Cubs regained a two-run cushion on a home run by Kosuke Fukudome in the sixth.
A single by Geovany Soto drove in the final run of the game in the eighth.
Vasquez (1-1) lasted six innings while giving up three runs on seven hits. He had recorded his first victory in the majors last Friday against Kansas City.
Chicago closed out a 10-game road trip with a 3-7 record. The Cubs open an 11-game homestand Thursday against Milwaukee.
Copyright 2009 by United Press International.