San Francisco used two interceptions returned for touchdowns to help stifle Drew Brees and the Saints offense.
Along with his two interceptions, Brees was sacked five times for 36 yards.
San Francisco quarterback Colin Kaepernik made the second NFL start of his career.
The rookie quarterback was 16/25 for 231 yards, throwing for one touchdown and running for another.
The win moves San Francisco to 8-2.
New Orleans continues a brutal three week stretch, that includes matchups with three straight division leaders.
The Saints will play NFC South rival Atlanta (10-1) on the road on Nov. 29th when they visit the Georgiadome for a Thursday night affair.
New Orleans beat the Falcons in week 11 at the Superdome by a score of 31-37.