Goaltender Brian Elliot kept the dangerous Blackhawks at bay with 29 saves, while the Senators (26-21-4) charged to a 2-0 advantage on first-period goals from Zack Smith and Ryan Shannon.
Marian Hossa replied for Chicago with a short-handed strike against his former team at 6:18 in the second but Peter Regin restored the two-goal cushion for the home team 12 minutes later.
Mike Fisher added the final goal on a snap-shot with 3:15 remaining.
The Blackhawks (34-12-4), who entered the contest tied with the San Jose Sharks on an NHL-leading 72 points, were beaten for the first time in four games.
(Writing by Jahmal Corner in Los Angeles; Editing by John O'Brien)