The Austrian-born winger had surgery on his injured jaw and will miss 3-4 weeks.
Vanek was injured at the 7:52 mark of the first period when he was struck on the right side of his face by a shot from Senators' defenseman Anton Volchenkov. After being hit, the left wing immediately grabbed his face and rushed to the locker room.
Sabres head coach Lindy Ruff said after the game that Vanek was in a good deal of pain.
"Right now, he's suffered a big laceration on his jaw," Ruff told the Buffalo News. "The teeth got pushed up a little bit but they are involved on the lower jaw part."
Vanek, the fifth overall pick in 2003, is currently the third-leading scorer in the NHL with 32 goals and was playing in his 225th consecutive game Saturday before being injured. He has missed just one game in his four-year career -- a healthy scratch against the Toronto Maple Leafs on Apr. 3, 2006.
Vanek is the second Sabres player in the last month to miss time because of a jaw injury. Defenseman Teppo Numminen missed six games because of a small bone fracture in his jaw sustained Jan. 17 against Carolina. Numminen was struck by a shot by Hurricanes defenseman Tim Gleason.
The 25-year-old Vanek was the first player in the league to score 20 goals this season and was on pace to eclipse his career-high of 43 goals scored in 2006-07. He notched his fifth career hat trick, and fourth natural hat trick, in Wednesday's win against Toronto, becoming just the second player in NHL history to have four consecutive natural hat tricks.
Cy Denneny of the old Senators was the other, accomplishing the feat during a 14-month period that began in February 1923.
Information from The Associated Press was used in this report.