The 26-year-old was solid from start to finish, including 16 saves in the first period to help his team jump out to a 3-1 lead after 20 minutes of play.
This marked the first time this season that the Sharks had been outshot in a game.
Both teams looked tired by the time the third period rolled around, despite the fact only the Sharks had played the night before.
The Senators lack of urgency proved costly as the Sharks scored two early third-period goals to put the game out of reach.
Sheppard scored his first of the season as he beat Anderson far side and Pavelski made it 5-2 after burying a big rebound.
Trailing 3-1 to start the second period, the Senators gave the home crowd something to cheer about when Methot closed the gap with a bullet from just inside the blueline.
Once again the Senators got off to a terrible start allowing the Sharks to jump out to an early 2-0 lead.
Hertl opened the scoring at 1:16 as the puck bounced over Senators' defenceman Joe Corvo's stick, allowing Hertl to quickly put it between Anderson's legs.
Just over five minutes later sloppy play by the Senators in their own end allowed Desjardins to make it 2-0 as he picked up a rebound and scored off his backhand.
Ottawa cut the lead in half midway through the period, as Karlsson was able to score through traffic. With Seantors' forward Cory Conacher creating a screen Stalock barely had a chance to see the shot until it was behind him.
Any momentum from the Ottawa goal was lost after giving up a short-handed goal with less than two minutes remaining in the period.
Karlsson bobbled the puck at his own blueline and San Jose's Logan Couture took off on a breakaway. While Anderson made the initial save the puck rested in the crease and Wingels banged it in to restore the two-goal lead.
This was the second and final meeting between the two teams this season.
Notes: Ottawa's LW Clarke MacArthur missed Sunday's game with what the Senators described as a minor injury, LW Matt Kassian and D Eric Gryba were healthy scratches for the Senators… San Jose remains without RW Brent Burns (puck in the mouth, day-to-day). RW Marty Havlat (pelvis, undetermined), and D Dan Boyle missed his sixth straight game. LW Matthew Nieto was a healthy scratch.