The victory also snapped the Cubs' nine-game winning streak.
For the record, the Padres (24-37) never did get a hit with runners in scoring position on Wednesday, as they threatened often against Cubs starting pitcher Ted Lilly, but managed to go 0-for-11 with runners in scoring position, stranding seven runners.
One swing took care of that, though, as Kouzmanoff atoned for his strikeouts in the first and sixth innings with runners in scoring position. He got even in the eighth, when the Cubs (38-22) lifted the left-handed Lilly in favor of right-hander Carlos Marmol.
Kouzmanoff's sacrifice fly drove in Giles, who doubled for the second time in the game to start the inning. Giles took third base when Adrian Gonzalez, hanging in against the left-handed Lilly, flied out to left field.
The Cubs went to Marmol, who two nights earlier allowed a three-run home run in the ninth inning to Gonzalez. Marmol first offered Kouzmanoff a slider low that the second-year third baseman laid off. He then jumped on a 94-mph fastball away to knock in Giles.
"Situational hitting," Padres manager Bud Black said. "He got the run in."
That two runs were actually enough to win against the Cubs -- who have scored the most runs in the Major Leagues -- merited some surprise, though Black liked his chances with 41-year-old Greg Maddux on the mound.
Maddux tamed an offense that had scored 16 runs in the first two games of the series, allowing just one run on three hits over seven innings. He didn't walk a batter, and had four strikeouts, to boot. He didn't get the victory but he was certainly a big reason why the Padres were able to take one game in this three-game series.
"Doggie threw the ball good and we never could get anything going, and made a lot of quick outs," Cubs first baseman Derrek Lee said. "He kept his pitch count down, and that's the last thing you want when he's on the mound.
"He's not going to beat himself. He's going to make you beat him. He threw strikes tonight, and we hit a ton of ground balls and that's what he tries to do."
As for Maddux, who has won just once since April 13, he was more interested in talking about his teammates and the victory than he was of himself.
"You do what you can not to lose -- that's what a starting pitcher does," he said. "I'm glad it didn't go extra innings."
The rate at which the Padres were struggling to get a clutch hit on Wednesday, you had to wonder if extra innings were inevitable.
Scott Hairston hit a leadoff home run in the first inning off Lilly but the Padres left Edgar Gonzalez (double) and Giles (walk) on base when Adrian Gonzalez hit into a double play and Kouzmanoff struck out.
The Padres had runners on the corners with one out in the second inning and still were unable to score. Then in the sixth inning, Giles led off with a double and moved to third base on a throwing error. But Kouzmanoff struck out, Giles was thrown out at the plate and Justin Huber flied out to the warning track in center field.
In the eighth inning, though, the Padres finally got a run across after Giles, who reached base three times, got the seventh hit of the game off Lilly (5-5), who struck out eight and walked two in 7 1/3 innings.
Heath Bell (3-3) picked up the victory with a scoreless eighth inning and Trevor Hoffman earned his 12th save of the season with three strikeouts in the bottom of the ninth inning.