Hampton (6-8) gave up six runs in the first inning, including a three-run homer to Alfonso Soriano. Seven of the first nine batters reached against Hampton, and the two Cubs batters who didn't reach in that span had a sacrifice fly and a sacrifice bunt.
"I think we just got to him early," Cubs first baseman Derrek Lee said. "The leadoff hitter gets on and [Ryan] Theriot hits a double and it's second and third right off the bat. The pitcher's in a tough position, and we were just able to capitalize and keep adding on."
With the shorthanded Astros bullpen having thrown 13 innings in the first two games of the series, Hampton had no choice but to try to endure as many innings as possible. Hampton, who is 0-3 with a 7.40 ERA in his last four road starts, lost at Wrigley Field for the first time since 1997.
"You try to go as long as you can go with your starter, especially at this point in time and all the innings we've had the last few days," Houston manager Cecil Cooper said. "I thought Mike kind of sucked it up for us a little bit, and you've got to do that. You hate to leave a guy out there and give up seven or eight runs, but you kind of didn't have a whole lot of choice."
Highly touted prospect Bud Norris replaced Hampton and worked three innings in his Major League debut, giving up one run. Doug Brocail, making his first appearance in a Major League game since May 3, allowed three hits and two runs in the eighth inning.
Meanwhile, Cubs starter Randy Wells (7-4) threw a career-high eight scoreless innings to win his third consecutive game. Wells, who held the Astros to four hits in six scoreless May 16 in Houston, didn't allow a runner to reach second base until the eighth inning.
"We got down early and he had a good lead early, which helps a pitcher out," Astros center fielder Michael Bourn said. "You can settle down and settle in when you have a big lead. It's a different ballgame if we stay with him a little bit better. He got out of some jams and had some double-play balls."
Second baseman Kaz Matsui (3-for-3) accounted for half of the Astros' six hits. Hunter Pence had a single to extend his hitting streak to six games, and Miguel Tejada went 1-for-4 and has hit safely in 19 of the past 21 games. All six of the Astros' hits were singles.
None of that mattered much, though, after Hampton's first-inning struggles. Opposing batters are hitting .443 against Hampton in the first inning of games this year. Aramis Ramirez hit a solo homer off him in the second, and the Cubs scored twice more in the fourth to make it 9-0.
"Most of his starts he's been able to get righted after giving up one or maybe two, and he'll go two or three innings where he throws the ball a lot better and keeps it down instead of giving them pitches to hit," Cooper said. "Today was kind of a tough day for him. He has some problems in the first innings. We have to figure out a way to get that right."