Thomas, shaking off a foot injury that had kept him out of his team's previous contest, gave an inspired effort, outdueling star Chargers running back LaDanian Tomlinson.
Chicago (3-5), which improved to 3-1 at Soldier Field, saw its lead dwindle to 13-7 after Doug Flutie replaced an ineffective Drew Brees and led San Diego to a touchdown drive, culminating in a three-yard run by Tomlinson with 9:12 remaining.
Thomas iced the game with a one-yard scoring run with 20 seconds remaining to ice the contest.
In his third straight start for the injured Kordell Stewart, Chris Chandler completed 21-of-30 passes for 224 yards and one interception for Chicago.
Brees went just 7-of-15 for 49 yards with an interception before being pulled early in the fourth quarter for Flutie, who went 8-of-11 for 70 yards.