Lilly (10-8) tossed eight scoreless innings, and Derrek Lee hit a two-run homer off Felipe Paulino (2-7), as the Astros fell to the Cubs, 2-0, and finished their trip 2-7. They have lost 19 of their last 25 road games.
The Astros scored six runs in three games against the Cubs, the same number they scored against the Cardinals from Aug. 25-27.
"Pretty hard to win like that," manager Cecil Cooper said. "Guys pitched well the first three games of this road trip. These last three were well-pitched games. We just couldn't generate offense, at least consistent offense, and you've got to have consistent offense in order to have a chance to win."
Houston's bats were unable to support Paulino, who was sharp in his first start since Aug. 4. Paulino has bounced between the starting rotation and the bullpen this season and has not excelled at either role, but he held the Cubs to two runs and struck out seven, mixing a hard fastball with a nasty slider.
It was Paulino's best outing since he held Detroit to one run and struck out nine on June 27. In two starts since, he had surrendered 13 earned runs in 6 1/3 innings.
"I thought Paulino did a terrific job pitching today," Cooper said. "He commanded the zone pretty good, and he had some nice sliders he threw today. I just thought he did a great job, and he just made the one mistake [to Lee], and I think if he had gotten that ball down, he probably would have gotten an out there, too. So just a good performance by a young man who is trying to establish himself."
Paulino cruised through three innings but gave up a leadoff double to Andres Blanco in the fourth. Two pitches later, he said he tried to throw a fastball sinking away from Lee, but the ball stayed up and out over the plate. Lee crushed it over the left-field wall for the 14th home run Paulino has allowed in 70 2/3 innings.
Lee was impressed with Paulino's location and said he was hitting the outside corner and throwing a sharp slider.
"He just left one over the middle," Lee said.
The two runs were plenty of support for Lilly, who gave up four hits and struck out five without walking a batter. After Hunter Pence led off the fourth with a double, Lilly retired the next 13 batters in a row until Humberto Quintero's bloop double with one out in the eighth.
Lilly responded by striking out pinch-hitter Lance Berkman and inducing a routine fly ball from Kaz Matsui. He now has racked up 19 2/3 consecutive scoreless innings against the Astros, dating back three starts.
"I think he's done pretty good against us every time," Pence said. "He's where he is because he knows what he's doing. He's just crafty. Everything is changing speeds, your eye level. We had some opportunities, and he pitched well."
Houston managed a rally against closer Carlos Marmol in the ninth. Michael Bourn pinch-hit to lead off the frame and grounded out, snapping his 25-game streak of reaching base, which was the longest active streak in the Majors. Pence followed with a walk, and Carlos Lee singled, but Miguel Tejada flied out and pinch-hitter Geoff Blum popped up to end the game.
"Marmol's tough," Cooper said. "You go down our lineup, and not many guys have hit him very well. I mean, we had a chance. That's all you can ask for is an opportunity."
Aside from Paulino's performance, the bright spot of the day for the Astros was that Aaron Boone made his 2009 debut after undergoing open-heart surgery in March. He contributed a sparkling play at first base, knocking down Jeff Baker's hard grounder and tossing to Paulino to end the second.
But like the rest of the Houston lineup, Boone had trouble against Lilly and went 0-for-3. The Astros had five hits as a team and finished their road trip with a .212 batting average. They have an off-day Thursday to regroup and then will begin a 10-game homestand Friday against the Phillies.
Andrew Simon is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.