David Pastrnak had a goal and an assist for the Bruins, Craig Smith, Jake DeBrusk and Greg McKegg also scored, and Jaroslav Halak made 23 saves.
Krejci became the eighth Bruins player to notch 700 points. He has 208 goals and 494 assists in 935 NHL games, all with Boston.
Smith, who joined the Bruins this season after nine years in Nashville, said playing with Krejci has been ''incredible.''
''He's one of the smartest players I've ever played with,'' Smith said.
Kyle Okposo scored his first career short-handed goal but it was hardly enough for the Sabres in their first game under new coach Don Granato. Buffalo's 13-game skid (0-11-2) is the second-longest in franchise history and the longest in the NHL since the Sabres lost 14 straight during the 2014-15 season.
''The bottom line is we need to go forward,'' Granato said. ''We need to demand more, obviously. Push harder, all of us. Coaches, players, everybody.''
The two-game series concludes Saturday in Buffalo, when up to 1,800 fans - 10% of building capacity - will be allowed to attend.
The game was allowed to proceed after both teams canceled their pregame skates due to members entering the NHL's COVID-19 protocol. Boston forward Sean Kuraly was added to the protocol list, while the Sabres did not disclose which member of their hockey staff had a positive test.
The Sabres' season has already been disrupted by a two-week pause after seven players and former coach Ralph Krueger spent time in the protocol in early February.
Krueger was fired Wednesday, but the coaching change did little to inspire the Sabres' performance. Buffalo extended its home losing streak to 10 games (0-9-1), the second-longest in team history after a 12-game skid in 1991.
The Bruins took the lead for good when DeBrusk scored on a power play midway through the second period. After drawing a high-sticking penalty on Buffalo's Matt Irwin, DeBrusk got to the front of the net, knocked down a high rebound from David Pastrnak's point shot and poked the puck past Hutton for his third of the season.
Krejci got his 700th point with a secondary assist on DeBrusk's goal. He then set up Smith in the slot to make it 3-1 late in the third period, and notched his third assist on Pastrnak's team-leading 14th goal on a power play in the fifth minute of the third period.
''He is going to get you the puck if you are a scorer,'' Bruins coach Bruce Cassidy said. ''If you are a shooter, find open ice and be ready if he's ready to dish it. That is Krejci's best attribute. His puck skills and vision.''
Okposo snapped a 30-game scoreless streak and tied the game for Buffalo with his shorthanded goal in the opening minutes of the second period. His shot from outside the right circle deflected off the stick of Boston's Matt Grzelcyk and fluttered over Halak's glove.
''I think we really got going after the shorty,'' Cassidy said. ''It was a bit of a lucky deflection. But guys got dialed in to getting back to playing our way.''
Carter Hutton stopped 33 shots for Buffalo.
McKegg, who replaced Kuraly in the lineup, tipped in Grzelcyk's shot to scored his first goal as a Bruin less than three minutes into the game.
Boston C Trent Frederic sustained a lower-body injury when he blocked a shot in the first period and did not finish the game. Postgame X-rays were negative, Cassidy said.
Bruins G Tuuka Rask is nearing a return from missing six gams with an undisclosed injury. Rask will be evaluated on Friday, Cassidy, and could play Saturday.
Buffalo recalled rookie D Jacob Bryson from the taxi squad Thursday, and Bryson tallied his first NHL assist on Okposo's goal.
BACK IN THE BUILDING
The Sabres invited more than 700 frontline workers and guests from Roswell Park Comprehensive Cancer Center to be the first fans in attendance at KeyBanker Center this season. They were honored during video tributes throughout the game as part of Hockey Fights Cancer Night.
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