Jake Locker threw a 34-yard touchdown pass to rookie Justin Hunter with 15 seconds left and the Titans rallied to beat San Diego 20-17 Sunday.
It was their first win over the Chargers for the franchise since 1992 when the team was in Houston.
The Titans (2-1) had lost nine straight to San Diego in a skid that spanned two states and two decades.
Locker ended the slide by completing seven passes to six different receivers for 94 yards on the game-winning drive.
He finished with 299 yards passing and also ran for 68 yards.
The Chargers' final play featured a handful of laterals and even a kick of the ball trying to keep it alive before the game ended.
San Diego (1-2) led most of the game despite having four starters out because of injuries and lost a fifth to an injured foot in the first half.