Ben Roethlisberger was unable to lead the Pittsburgh Steelers to victory in his first game for almost a month.
The San Diego Chargers led 13-3 at half-time, with Danario Alexander catching a 39-yard pass from Philip Rivers for a touchdown.
Two more touchdowns early in the third quarter saw the Chargers take a 27-3 lead.
Roethlisberger, who missed three games with rib and shoulder injuries, threw three touchdown passes late in the game as a consolation for the Steelers.
The 34-24 loss means that the Steelers failed to close the gap on AFC North leaders the Baltimore Ravens, who also lost yesterday.