Zambrano gave up two hits and a season-high five walks in 6 2-3 innings. He struck out seven while reaching the milestone in his third try since beating Florida on May 3 for win No. 99. Since then, he spent 19 days on the disabled list with a left hamstring strain, lost at San Diego and was suspended six games for an altercation with plate umpire Mark Carlson on May 27 in Chicago.
His return was delayed one more day by rain that washed out his scheduled start Thursday in Atlanta.
The Cubs pushed across a run in the first on Ryan Theriot's one-out infield hit
- one of his two hits after going 1 for 10 on he road trip with three walks.
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Zambrano (4-2), who struck out the side in the first, hit his second home run of the season and 18th of his career on Micah Owings' first pitch of the fifth inning, extending the Cubs' lead to 2-0.
After allowing his first hit in the bottom of the fifth, the right-hander struck out Owings before right fielder Micah Hoffpauir made a tumbling catch of Jerry Hairston Jr.'s drive to the warning track to end the inning.
Zambrano also helped his cause with some alert defense. He covered first base on Brandon Phillips' foul pop near the first base stands in the sixth inning. First baseman Derrek Lee caught the ball and threw to Zambrano to double Chris Dickerson off of first.
In the seventh, with Jay Bruce on first and one out, Zambrano made a juggling catch of Alex Gonzalez's line drive up the middle. Zambrano was replaced by right-hander Angel Guzman after walking the next batter.
Owings (3-7) left after allowing five hits and two runs with three walks and a season high-tying six strikeouts in six innings.
Phillips broke up the shutout with a one-out RBI triple off of reliever Carlos Marmol in the eighth inning, snapping Cincinnati's streak of consecutive scoreless innings at 16. Marmol recovered to get Laynce Nix to pop up. Ramon Hernandez walked, but Bruce grounded out to strand Phillips at third with the potential tying run.