Bears star pass-rusher Khalil Mack set up a touchdown with a strip-sack of Giants quarterback Daniel Jones, while wideout Allen Robinson recorded a season-high 131 receiving yards and a score to give Chicago (5-6) its second win in three games.
The Giants (2-9) lost their seventh straight game and clinched their third consecutive losing season with Sunday's defeat.
New York grabbed a 7-0 lead midway through the first quarter after Kaden Smith hauled in a 3-yard touchdown pass from Jones. Eddy Pineiro converted a 26-yard field goal before the end of the first to cut the Bears' deficit to 7-3.
Bears quarterback Mitchell Trubisky tossed a 32-yard touchdown to Robinson early in the third quarter and Pineiro added a 24-yard kick to boost their lead to 13-7.
Mack notched only his second sack in seven games when he brought down Jones deep in Giants territory and stripped the ball. Bears defensive lineman Nick Williams recovered the fumble, which led to a 2-yard touchdown run by Trubisky to make it 19-7 late in the third quarter.
The Giants cut the lead to five with 4:10 remaining in the game after Golden Tate came down with a 23-yard score on fourth-and-18. Chicago went three-and-out before punter Pat O'Donnell pinned the Giants at their own 6-yard line, and the Bears held on to seal the victory.
Trubisky completed 25-of-41 passes for a season-high 278 yards. He had one touchdown pass and threw two interceptions.
Jones was 21-of-36 for 150 yards and two touchdowns. Giants star running back Saquon Barkley had 17 carries for 59 yards and two receptions for one yard.