Rookie Keenan Allen had a career-high nine receptions for 107 yards and a touchdown for the Chargers, who improved to 3-3 on the National Football League season.
Quarterback Philip Rivers was 22-of-33 for 237 yards and a touchdown and running back Ryan Mathews rushed for 102 yards on 22 carries for the Chargers, who totalled 147 yards on the ground in the win.
Andrew Luck completed 18-of-30 passes for 202 yards with an interception for Indianapolis, who will welcome quarterback Peyton Manning back to town on Sunday as the Colts host the Denver Broncos. The first place Colts lost just their second game on Monday to go with four wins.
Reggie Wayne became the ninth NFL receiver to reach 1,000 career receptions in defeat. He caught five passes for 88 yards.
The Chargers completed a 15-play, 74-yard drive that took 9:13 off the clock with a 34-yard field goal from Novak that gave them a 16-6 advantage with 9:43 left in the fourth.
The Chargers are now 16-9 overall over the Colts in the regular-season, but are 5-6 against them at home.
The Colts, who had a three game win streak snapped on Monday, had outscored their opponents by 54 points in their first two road games this season.