Paulino struck out seven in eight effective innings, Berkman drove in two runs and the Astros beat Zambrano and the Cubs 3-1 on Friday night for their fourth straight win.
Paulino (1-7) allowed one run and five hits to record his first victory since Oct. 1 at Philadelphia. The Astros averaged 1.97 runs in the first 10 games started by the 26-year-old right-hander this season, the lowest support in the majors for any regular starter.
Led by Berkman and Michael Bourn, who had three hits and scored twice, Houston finally managed to get Paulino some runs.
"It felt good," said Paulino, who threw 120 pitches. "Everything calmed me down. They just tried the best they could, and everything came together."
Matt Lindstrom pitched a perfect ninth to earn his 12th save after blowing his previous two chances.
Paulino improved to 1-1 with a 1.61 ERA in his last four starts, and the Astros were relieved they finally produced for him.
"He's pitched a lot better than his record would indicate," Berkman said. "It seems like every time he goes out there, he keeps us in the game and gives us a chance to win. We just hadn't been able to score any runs for him."
The Cubs have lost four in a row and scored only one or two runs in six of their last seven games. Cubs manager Lou Piniella promised changes for Saturday's game, including putting rookie Tyler Colvin in the lineup.
"I've been patient enough watching," Piniella said. "I know these guys are trying, but we see the same thing every day, day in and day out."
Zambrano (1-4) allowed three runs and six hits over 4 1/3 innings in his first start since April 20. The $91.5 million right-hander was moved to Chicago's shaky bullpen after opening the season with a 1-2 record and a 7.45 ERA in four starts.
Zambrano was 2-0 with a 0.90 ERA in four previous starts against the Astros, including a no-hitter in September 2008, but he struggled with his control early on, leading to a short outing.
Bourn led off the first with a single, advanced on Jeff Keppinger's groundout and scored on Berkman's drive to the left-field corner. Left fielder Alfonso Soriano threw the ball to the infield in time for the Cubs to catch Berkman in a rundown between first and second.
Houston loaded the bases when Zambrano gave up a double to Carlos Lee and two-out walks to Cory Sullivan and Geoff Blum. Pitching coach Larry Rothschild visited the mound, and Pedro Feliz popped up to end Zambrano's 34-pitch inning.
"Location was a problem," Zambrano said. "I felt too rushed, especially in the first inning. Larry talked to me, especially in the second and third inning, and said just lift my leg and drive to the plate with my arm, and that would help it. That was what it was. Problem was location."
Paulino escaped a bases-loaded jam in the third when Aramis Ramirez fouled out to Berkman to end the inning.
The Cubs had a scare in the fifth when rookie shortstop Starlin Castro was shaken up sliding into third on Zambrano's bunt up the third-base line. Third baseman Feliz threw out Zambrano and catcher Humberto Quintero ran to third to take the throw from first. Quintero and Castro collided, and Castro stayed down as Piniella and the Cubs' medical staff came out to check on him.
Castro remained in the game and scored on Marlon Byrd's double to the left-field corner. He had scrapes and cuts on his right forearm and left shoulder, but said he was OK.
Bourn singled in the bottom half, stole second and scored on Keppinger's single. Bourn leads the NL with 18 stolen bases.
Piniella then replaced Zambrano with left-hander Tom Gorzelanny, who was making his first relief appearance after nine starts this season. Berkman drove Gorzelanny's first pitch off the left-field scoreboard for a double to give Houston a 3-1 lead.
Paulino struck out at least one hitter in every inning between the fourth and the eighth. Bourn helped Paulino with a sharp defensive play in the seventh, chasing down Mike Fontenot's drive to the warning track in left-center.
The Cubs are 3-23 when scoring three runs or less. ... Sullivan started in right field in place of Hunter Pence. Pence was hitting .395 with three homers in his last 11 games, but had a .227 lifetime average against Zambrano. Pence replaced Sullivan in the fifth to face Gorzelanny. ... Piniella adjusted his upcoming rotation after Wednesday's game in Pittsburgh was postponed until Monday. RHP Ryan Dempster (3-5, 3.72 ERA) will start Saturday's game and RHP Randy Wells (3-3, 4.40 ERA) is slated to start Sunday's finale. Carlos Silva (7-0, 3.12 ERA) will start the makeup game against the Pirates.