Eli Manning's frustrations continued after the Bears won the toss at Soldier Park and deferred, putting the Giants in to start on offense.
The 32-year-old threw his 13th interception of the season when trying to find Hakeem Nicks, with Zack Bowman making the play and running it back to the 15, although the Giants defended well to prevent the home side taking the lead.
Manning was not to face a reprieve for throwing his second interception, as this time Tim Jennings cut out his throw to run in a 48-yard touchdown.
The Giants were level before the end of the first quarter thanks to Brandon Jacobs powering through from three yards, but Marc Trestman's side retook the lead 42 seconds into the second quarter when Jay Cutler found Brandon Marshall.
Once again the Giants roared back, with Manning picking out Rueben Randle to weave his way across the line.
However, Cutler and Marshall combined once again before Robbie Gould kicked a field goal to see the Bears lead at half time.