Pittsburgh-area native Neil Walker hit a two-run homer to the deepest part of the ballpark in left-center to put the Pirates ahead in the eighth and they beat the Cubs for the seventh time this season, 3-2 on Tuesday.
Walker, the Pirates' first-round draft choice in 2004 who went to the high school that won the Western Pennsylvania district championship Tuesday night, hit a 0-1 pitch from Ted Lilly (1-5) with Andrew McCutchen on and one out.
"This goes back to being 5 or 6 years old at Three Rivers Stadium, sitting in peanut heaven," Walker said. "Getting drafted by the Pirates, this is just a Cinderella story. It's incredible."
The Pirates improved to 7-1 against the Cubs this season -- they're 15-30 against everyone else -- and have won nine of their past 10 against Chicago overall.
Xavier Nady -- one of several backups in the Cubs lineup -- had four hits, including his third home run, but Chicago lost for the fourth time in five games.
Pittsburgh's Garrett Jones homered for the second consecutive day, Joel Hanrahan (2-1) pitched a perfect top of the eighth and Octavio Dotel a perfect ninth for his 12th save.
"It's a great moment for Neil, a hometown kid hitting his first home run like that, putting us ahead in the eighth," Pirates manager John Russell said. "We're very excited for him. It's something he'll never forget."
Cubs manager Lou Piniella, trying desperately to find a lineup that will produce consistent offense, juggled his starters again. Chicago had scored only nine runs in its previous four games.
No fewer than four Cubs regulars did not start - and that doesn't even include Ryan Theriot, who was recently benched for Mike Fontenot at second base. Nady started for Derrek Lee at first, Jeff Baker replaced Aramis Ramirez at third, Tyler Colvin played center over Marlon Byrd and catcher Geovany Soto sat in favor of Koyie Hill.
Before the game, Piniella philosophized about his offense and how he "clings" to the hope of it turning around. Afterward, he was in no mood to discuss much of anything.
"I am not going to talk about it anymore," he said after less than two minutes with the media. "We just got beat, come out and get them tomorrow and do the best we can, that's all we can do."
The lineup shuffle seemed to pay off when Nady homered with Kosuke Fukudome aboard and one out in the third. It gave Chicago a 2-0 lead and twice as many runs as it had scored in four of the previous five games.
"This is frustrating for everyone," Nady said. "You obviously come prepared and plan on getting big hits and getting things going, but offensively, we're just not doing it. There's no way around it."
The Cubs' most recent three wins had come by shutout. Jones erased that possibility when he led off the fourth with his seventh home run.
An inning prior, Pittsburgh had an apparent run taken away when Lasting Milledge was thrown out trying to stretch his two-out hit into a triple before starting pitcher Jeff Karstens crossed home plate.
For a team with its own offensive troubles -- the Pirates, at 15th, rank two spots below the Cubs in the National League in runs -- wasting an opportunity to score appeared too much to overcome until the eighth.
Lilly hadn't officially pitched more than seven innings since September, but threw a season-high 112 pitches Tuesday.
"We needed just one more out from Lilly," Piniella said. "We didn't get it. He pitched a good ballgame."
After one out in the eighth, Lilly walked McCutchen before Walker hit his fastball into the seats to give him at least one hit in six of his eight games since being called up last week.
"I don't know if I can compare this to anything that's ever happened to me," Walker said. "Maybe the day being drafted? I'm really at a loss for words, and I'm usually not at a loss for words. I'm just tremendously happy."
Making his first start since May 8, Karstens allowed two runs on six hits in six innings.
After the game, Pittsburgh announced it was activating LHP Jack Taschner from the disabled list and sending RHP Steven Jackson to Triple-A Indianapolis. ... The Pirates had at least one home run for the fourth game in a row, a season high. ... Lilly has gone at least six innings and allowed three earned runs or less in each of his past five starts.