Brandon Sutter had a goal and two assists, and Stephane Yelle and Ray Whitney also scored for Carolina, which gave coach Paul Maurice his 400th career victory by continuing its sharpest stretch of the season.
The Hurricanes are on their second four-game winning streak, have eight wins in 10 games and claimed their fifth straight victory at home.
The decisive sequence started when defenseman Steve Montador slipped while trying to play the puck near goalie Ryan Miller. Sutter snatched it and backhanded a pass to a cutting Samsonov, who snapped it past Miller.
Derek Roy scored two goals and Jochen Hecht added one for Buffalo, which has lost six straight for the first time since an 0-5-5 stretch in 2007-08. The Sabres will host Western Conference-leading San Jose on Saturday in their final game before the Olympic break.
Yelle gave Carolina a 3-2 lead with 10:05 left in the second, when he skated down the right side and whipped a shot past Miller's shoulder and into the upper-left corner of the net for his second goal since Nov. 27. Roy tied it with 7:07 left in the third by beating Manny Legace with a backhander.
Miller, the probable starter for the United States in the Olympics, made 31 saves.
Legace stopped 29 shots and improved his career record against Buffalo to 5-0 by beating the Sabres for the second time in a week.
Carolina used a suddenly productive power play to erase an early 2-0 deficit, scoring twice with the man advantage in a 3 1/2-minute span against the NHL's best penalty kill.
Sutter got things started for the Hurricanes by beating Miller with a wrist shot, and Whitney took a pretty feed from Jussi Jokinen and chipped the puck over the Buffalo goalie's shoulder with 1.3 seconds before the break.
That came after the Sabres jumped on Carolina early. Roy put his team's first shot in the net and Hecht stretched the lead to 2-0 with a flukey goal that appeared to click off Hurricanes forward Steven Goertzen and through Legace's legs.
It was Sutter's first career three-point night. ... Jokinen extended his points streak to eight. ... Roy has four goals in six games. ... Ruutu reached 200th career points with an assisted on Carolina's first goal.