Hoping to end a century-long streak without a World Series title, the Cubs took an early 2-0 lead. But the Wrigley Field crowd was silenced by Loney's homer, the first of three blasts from the Dodgers.
Chicago pitchers walked eight batters, seven by starter Ryan Dempster, and the Cubs' offense went cold after a two-run homer by Mark DeRosa in the second inning.
The Dodgers, who took part in their first playoff game under Manager Joe Torre, will try to grab a two-game lead in the National league Division Series Thursday.
"This is where we want to be," said Loney, who hit 13 regular-season homers. "We want to finish this thing as soon as possible."
Dempster walked four batters over the first four innings without giving up a run, but wildness led to his undoing in the fifth. He walked Rafael Furcal, Manny Ramirez and Andre Ethier to load the bases with two out before Loney sent a 1-2 pitch over the wall in center.
Ramirez, whose trade to Los Angeles from Boston in the midst of the season sparked the Dodgers to a division title, also homered in the seventh. Russell Martin added a solo shot in the ninth.
Starter Derek Lowe got the win, giving up two runs on seven hits over six innings while striking out six. Dempster, who had a 17-6 record during the regular season, lasted only 4 2/3 innings.