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Joe Flacco went 23-for-34 through the air for 226 yards and two scores, but was intercepted twice in the third quarter as the Ravens (10-4) had their four-game win streak snapped.
Ray Rice carried the ball 10 times for 57 yards while also hauling in nine passes for 55 yards in a losing effort.
Baltimore received the ball first and quickly moved down the field on a 22- yard run by Rice and a 33-yard reception by Anquan Boldin, but the drive stalled at the San Diego 18 and Billy Cundiff's 36-yard field goal attempt sailed wide right.
Baltimore responded with a 13-play, 75-yard drive that stretched into the second quarter to tie the game at 7-7. Rice carried the load on the march, reeling off six runs for 30 yards before Flacco found Ed Dickson for a 15-yard score.
Nick Novak split the uprights from 45 yards out to put the Chargers up by three before Vincent Jackson's 58-yard reception down the left sideline set up Mathews' one-yard TD run in the final minute of the second quarter.
The Ravens then drove into San Diego territory to try and answer, but Flacco failed to see Chargers linebacker Takeo Spikes on a pass over the middle and Spikes picked the ball off, returning it across midfield.
The turnover resulted in Mathews leaping over the line of scrimmage and into the end zone for a three-yard touchdown and a 31-7 Chargers lead.
Novak's 28-yard kick was true on the Chargers' next touch to put San Diego up by 27 before a 36-yard catch-and-run by the Ravens' Torrey Smith late in the game accounted for the final margin.
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Home Season Pound Crush On Uefa
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Percent Shooting Recalls Goal Efficiency On Points
MySportsbook.com favors Bears, Bengals, Chargers and Colts to remain perfect
LAS VEGAS , Sept. 28 - Two big match-ups of undefeated teams have fans salivating at the Week Four schedule in the NFL. The Chicago Bears stifling defense looks to provide a less than hospitable welcome to the Seattle Seahawks on Sunday night in a battle of two 3-0 teams in the NFC conference. In the AFC, the San Diego Chargers (2-0) head to Maryland to face the surprising Baltimore Ravens (3-0) as both try to keep pace atop the conference standings. Betting Lines makers at MySportsbook.com, online sportsbook and casino, have set the Bears as 3.5 point favorites while the Chargers are a 2.5 point bet.
Of the three remaining undefeated teams, only one, New Orleans, enters this week's game as an underdog. Despite an emotional and resounding win over Atlanta on Monday night, the Saints are a 7.5 point underdog against the struggling Carolina Panthers. Indianapolis looks to stay perfect when they face the New York Jets as a 9 point road favorite while the Cincinnati Bengals are a 6 point favorite at home to the New England Patriots.
Six teams enter the week still looking for their first win, with a seventh, Tampa Bay, on a bye week. The prospect of dropping another game would not bode well for a potential playoff run. Since 1990, just three teams -- the 1992 Chargers, 1995 Detroit Lions and 1998 Buffalo Bills -- have overcome losing their first three games of the season to earn a postseason berth. And only the Chargers managed to accomplish the feat after starting 0-4.
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