Patrick Mahomes led the Chiefs, completing 22 of 37 passes for 224 yards and a touchdown, and made a crucial recovery of his own backward pass.
The Chiefs' victory prevented them from an 0-3 start, a record they had not seen since 2011.
The New York Giants fell to 0-3, with quarterback Russell Wilson throwing two interceptions and facing boos from the crowd due to offensive struggles.
Giants coach Brian Daboll acknowledged the team's poor performance, particularly their inability to convert on third downs, stating, "On offense, nothing was good enough. I would be booing too."