Fullback Mike Tolbert accounted for three ahead score in the fourth quarter that sent the 17 victory over the Vikings.
Tolbert rushed for one touchdown and caught two from Philip Rivers, who finished with 335 yards on 33-of-48 passing, with two interceptions. Rivers' 19-yard connection with Tolbert provided San Diego (1-0) with its first lead of the game.
Tolbert hobbled off the field later in the game with an apparent leg injury, but his performance was a big factor in the Chargers starting the season with a win. They were 9-7 last year and missed the playoffs for the first time since 2005.
"It's a long game, but you've got to keep grinding, got to keep doing your thing," Tolbert said. "It's going to work out for the best if you win the most plays."
Percy Harvin gave the Vikings (0-1) the lead with a 103-yard return on the game's opening kickoff, and Minnesota went into halftime with a 17-7 lead.
But the Vikings were shut out in the second half, when new quarterback Donovan McNabb was largely a non-factor. He was acquired from Washington during the offseason, but finished with just 39 yards on 7-of-15 completions, with one touchdown and an interception.
"We didn't help ourselves out. There were opportunities in the game we should have taken advantage of," McNabb said. "We just couldn't get in rhythm like we needed to."
Minnesota is trying to rebound from a disappointing 2010, when it went 6-10.
But the Vikings gained only 26 yards during the second half and watched their lead disappear in the fourth quarter.
San Diego's game-winning drive started at its own 36 with 8:11 to play and the contest tied. Ryan Mathews ran for 11 yards on the first play, and an unnecessary roughness penalty on Minnesota pushed the ball into Vikings territory.
Rivers converted a third down with a 13-yard pass to Antonio Gates, bringing the ball to the 19.
Two plays later, Rivers scrambled to his left as the play developed, then found Tolbert along the sideline. Tolbert grabbed the pass and dove to get the ball across the goal line.
The advantage was safe because of Minnesota's inability to gain yards. The Vikings actually lost 10 in going three-and-out -- McNabb was sacked on his final play of his Vikings debut -- and San Diego ran the rest of the time off the clock to secure the win.
Harvin's return got the Vikings off to a good start in Sunday's game. He cut to the right side of the field early in the run to avoid a wall of Chargers, then broke a tackle and turned upfield, sprinting past several more.
His decisive move was a cut back toward the middle of the field, where there was open space and little chance of someone catching him. He was past every San Diego player with 30 yards to go and cruised into the end zone.
Making matters worse for the Chargers was the fact that kicker Kaeding suffered a left knee injury during the return.
But Minnesota's momentum was quickly gone. McNabb's first pass as a Viking was intercepted by Shaun Phillips, and three plays later Rivers hit Tolbert with a one-yard TD throw.
The Vikings did put together a long drive, which started at their own two-yard line and spanned the first two quarters. They went 77 yards, but the march stalled deep in San Diego territory and Ryan Longwell kicked a 33-yard field goal.
San Diego went three-and-out on its next possession, allowing the Vikings to take over at their own 49-yard line. They scored again, thanks to a 46-yard run by Adrian Peterson. That set up McNabb's three-yard TD to Michael Jenkins with 9:44 left in the half.
The Chargers faced the 17-7 deficit at the break after their next two drives were unsuccessful. They turned the ball over on downs during a drive that lasted more than six minutes, and Rivers was intercepted in the final minute with the ball deep in Vikings territory.
But San Diego's offense came to life in the second half, scoring on three of five possessions.
The Chargers opened the third quarter with a seven-play, 69-yard drive that Tolbert capped with a seven-yard run. Their next touch ended with an interception, but they tied the game with 10:05 left in the game on a 40-yard field goal by Scifres.
Harvin recorded his fourth career kickoff return for a touchdown...Minnesota gained only 187 yards, including just 26 in the second half...Peterson finished with 98 yards...Scifres' field goal was his first career try...McNabb finished with a quarterback rating of 47.9. He passed for two yards in the second half.