Stastny and Hejduk spearheaded a Colorado surge that made coach Joel Quenneville's shakeup of the Avs' four lines look wise.
The Avalanche's top line had failed to post a point in the first two games but had little trouble contributing against the Sharks, as captain Joe Sakic had a goal and assist to move past Phil Esposito into eighth on the NHL career points list with 1,591.
Stastny, the runner-up to Pittsburgh's Evgeni Malkin for rookie of the year honors last season, has four goals and four assists in Colorado's first three games. He had a hat trick in the Avalanche's season-opening win against Dallas on Wednesday.
"I don't think they're coming easy. I've gotten a couple of good bounces," said Stastny, who had 28 goals and 50 assists last season. "I'm playing with some good linemates."
Hejduk scored late in the first period, less than three minutes after Sakic notched the 611th goal of his 19-year career. Sakic's goal moved him out of a tie for 14th place with Bobby Hull on the career list.
"Obviously, I've been around a long time," Sakic said. "For me to have played this long and get to those guys who meant a lot to the game, it's an honor."
The Avalanche poured it on in the third after Ryane Clowe scored the first of his two goals to make it 2-1 after two periods. Just 52 seconds into the final frame, Hejduk found Stastny in front to give Colorado a two-goal cushion.
"I thought last year he was at a pretty impressive level, and to just keep getting better is a great sign," Quenneville said. "With the puck, his patience level is at the highest end of the game."
"We were pushing the pace in the second, and we were aggressive and going down and they didn't have much," Nabokov said. "The third period starts, and we give up a 3-on-2, and that made the momentum for them."
The Sharks played from behind most of the game in part because of four penalties in the first period, two whistled simultaneously. Marc-Edouard Vlasic and Jeremy Roenick were sent off with 5:05 left in the first period, and it took only 23 seconds for the Avalanche to cash in on the 5-on-3 advantage. Sakic fed Stastny down low, then one-timed the return pass to open the scoring.
Only 14 seconds after Joe Thornton drew a holding penalty, Sakic fed Hejduk, who made it 2-0 with a shot that beat Nabokov on the short side.
"We have to play better without the puck, and we just didn't compete," San Jose coach Ron Wilson said. "When you are that sloppy you are going to get embarrassed, and we were."
Avalanche goalie Peter Budaj, who had 24 saves, came up big after Hejduk drew a double minor for high-sticking 1:12 into the game. The Sharks had five shots during the four-minute power play, including a point-blank chance by Roenick, but failed to score.
Avalanche D Scott Hannan faced his former team for the first time since signing with Colorado in the offseason. Hannan play eight seasons for the Sharks. ... Roenick is three goals shy of 500 in the NHL. ... The last Avalanche player to score five points in a game was Sakic, who did it Feb. 15, 2007, at Calgary.
Copyright by STATS LLC and The Associated Press
Arena: Pepsi Center Location: Denver, Colorado
Referees: Steve Kozari, Kelly Sutherland Linesmen: Dan Schachte, Jay Sharrers
Attendance: 15,876 (88.2% full)
Team Stat Comparison
Power Play Goals
Power Play Opportunities
Shots on Goal
Joe Sakic (1)
(Power Play) Assists: Paul Stastny, John-Michael Liles
Milan Hejduk (2)
(Power Play) Assists: Joe Sakic, Paul Stastny
Ryane Clowe (2)
Assists: Joe Pavelski, Christian Ehrhoff
Paul Stastny (4)
Assists: Milan Hejduk, Jordan Leopold
Milan Hejduk (2)
Assists: Ryan Smyth, Paul Stastny
Marek Svatos (1)
Assists: Jeff Finger, Tyler Arnason
Ryan Smyth (1)
Assist: Paul Stastny
Ryane Clowe (2)
(Power Play) Assists: Steve Bernier, Matt Carle