The Chargers moved into field goal range in the game's final minute, but instead of attempting to tie the game they tried to pick up a first down on fourth-and-6 from the 22-yard line. Tramaine Brock ended the San Diego threat by intercepting a short pass by Jonathan Crompton.
San Francisco took a 10-0 halftime lead on a 46-yard run by Anthony Dixon and Joe Nedney's 25-yard field goal.
San Diego built a 14-10 advantage heading into the fourth quarter on a 93-yard punt return from Jeremy Williams and a 2-yard scoring run by Curtis Brinkley.
The 49ers will open the regular season in Seattle and San Diego starts out with a Monday night game in Kansas City.