Brett Myers pitched eight strong innings to earn his first win since moving back into the starting rotation. Myers (1-1) allowed three runs on solo homers, five hits and struck out five.
Derrek Lee, Aramis Ramirez and Alfonso Soriano connected off Myers, who finished last season as Philadelphia's closer.
The Phillies won without shortstop Jimmy Rollins for the first time in three tries. The 2007 NL MVP hasn't been in the starting lineup since he sprained his left ankle Tuesday.
Brad Lidge pitched a scoreless ninth for his second save.
Carlos Zambrano (1-1) gave up five runs and nine hits in six innings. Zambrano pitched on regular rest, even though he moved up a day after Jason Marquis was scratched Thursday because of illness.
Ryan Howard lined a double to left-center to start the bottom of the sixth against Zambrano. Burrell, trying to hit the ball the opposite way to move Howard, ripped an RBI double to right field to put the Phillies ahead 4-3. Carlos Ruiz added an RBI single to make it 5-3.
Burrell is batting .519 (14-for-27) with six homers and 12 RBIs in his last nine games against the Cubs. He leads the Phillies with four homers and 12 RBIs this season.
A questionable call allowed the Phillies to take a 3-2 lead in the fifth. After Shane Victorino drew a two-out walk, Greg Dobbs hit a drive that center fielder Kosuke Fukudome chased down in the alley. But Fukudome dropped the ball after running into left fielder Soriano and Dobbs was ruled safe, allowing Victorino to score on the double.
Cubs manager Lou Piniella came out to argue because Fukudome took two steps before the ball fell out of his glove. He walked away scratching his head after listening to third base umpire Tim Welke's explanation.