DeJesus had a solo home run in the Cubs' three-run third inning and a two-run shot in the fourth when Chicago built a 6-1 lead and beat Bud Norris (5-10).
Norris also gave up a two-run home run to Starlin Castro in the third. The Cubs battered him for eight hits and six runs in 3 1/3 innings. He walked three and struck out four.
Chicago starter Justin Germano (2-2) benefited from the Cubs' offense. He allowed just five hits, both Houston runs and one walk in 6 1/3 innings.
The Astros led 1-0 after Scott Moore led off the second with his seventh home run of the season. But Castro scored on a Brett Jackson triple in the bottom of the inning, and home runs by DeJesus and Castro highlighted the Cubs' three-inning rally in the third.
DeJesus had his second home run the next inning, giving him four homers this year and putting Chicago ahead 6-1. Jackson scored on a passed ball in the sixth for the final Cubs run.
Houston's second run came in the seventh when Moore scored on what ended up being a double play.