MacKinnon had a goal and two assists and J.T. Compher scored a power-play goal 3:25 into overtime to give the Avalanche a 4-3 victory over the Toronto Maple Leafs on Friday night.
Alexander Kerfoot and Mikko Rantanen also scored for Colorado and Semyon Varlamov had 31 saves for the Avalanche, who bounced back from losing to Arizona on Wednesday to beat another Eastern Conference power.
Colorado swept two-time reigning champion Pittsburgh and split the season series with Washington.
MacKinnon was a big reason for the Avalanche's win Friday. His three points gives him 43 for the season, which is ninth among NHL scorers. He also drew a penalty on Connor Brown in overtime that led to the winner.
"MacKinnon, when he's on like that, he's a lot to deal with for opposing teams," Colorado coach Jared Bednar said. "Tonight he was great."
Pickard was recalled Friday night and flew to Denver to meet his team. His first NHL game this season came against his former team and friends, and he chatted with MacKinnon throughout the game.
"We were talking a lot of the game. He's one of my good friends, and that first line, we're all really close," Pickard said. "It's too bad they were feeling it tonight. We were kind of jawing at each other, all fun and games. It's good to see (MacKinnon) doing well."
The Avalanche got a break in overtime when Brown was given a minor for interference. Colorado had several chances, including MacKinnon hitting a post, before Compher beat Pickard with 9 seconds left on the power play.
"I'm disappointed about going shorthanded in overtime, especially with the amount of calls that could have been made," Toronto coach Mike Babcock said. "That one shouldn't have been made."
The Avalanche took a 3-2 lead when Kerfoot scored his 10th goal of the season at 4:34 of the third period. Toronto pressured for the tying goal and finally got it when Van Riemsdyk scored at 18:05 with Pickard off for an extra skater.
Colorado's top line of MacKinnon, Rantanen and Gabriel Landeskog held Toronto star Auston Matthews without a point, although he had several good chances. Matthews has earned praise for his in less than two full seasons, but MacKinnon feels he has played himself into the conversation as one of the best young players in the league.
"As a top young guy I feel like I am," MacKinnon said. "I'm kind of living in my own bubble and focused on what I have to do and what the team has to do. I'll let everyone else decide those things."
MacKinnon gave Colorado a 1-0 lead with his 16th goal midway through the first period. Toronto tied it when Martin's centering pass from down low bounced of Blake Comeau's skate and in at 14:55.
Rantanen again gave Colorado the lead with his one-timer on a pass from behind the net from MacKinnon at 10:29 of the second period. It was Rantanen's 12th of the season. Toronto quickly answered when Polak's soft shot from a sharp angle beat Varlamov at 14:04.
NOTES: Rantanen has points in eight straight games, the longest streak of his career. ... Toronto C Nazem Kadri was scratched with an upper-body injury. Kadri has 13 goals and 10 assists but has not recorded a point in 11 straight games. ... The Avalanche recalled D Andre Mironov from San Antonio of the AHL on Thursday. He was a healthy scratch Friday. ... Pickard was recalled from the AHL because backup Curtis McElhinney is out with a lower-body injury. ... Colorado has not allowed a power-play goal in its last 10 games. The Avalanche have killed off 30 straight penalties in that span.
Maple Leafs: Make their first trip to Vegas to play the Golden Knights on Sunday.
Avalanche: Host the New York Islanders on Sunday night.