MacKinnon was signed to his first NHL contract, a three-year entry level deal, with the Avalanche on July 9, 2013.
MacKinnon made his NHL debut to begin the 2013–14 season on October 2, 2013, becoming the youngest hockey player to ever dress in a regular season game for the Colorado Avalanche franchise, registering two assists in a 6–1 victory over the visiting Anaheim Ducks.
MacKinnon scored his first NHL goal October 12, 2013, against Michal Neuvirth of the Washington Capitals during the second period at the Verizon Center.

During the season MacKinnon's role increased, as he was placed on the top two offensive lines.
He claimed his first NHL record in becoming the youngest player to record back-to-back two-goal games from January 4–6, 2014, beating Dale Hawerchuk's of the original Winnipeg Jets from 1981.
MacKinnon later compiled a 13-game point streak from January 25, to March 6, surpassing Wayne Gretzky (who turned 19 during his first season) to have the longest scoring streak by an 18-year-old in NHL history.
MacKinnon finished the regular season appearing in all 82 games and led all rookies with 24 goals and 39 assists for 63 points.
MacKinnon became just the third player in the NHL to record seven points in his first two playoff games with a goal and six assists in the first two contests against the Minnesota Wild in the opening round of the 2014 Stanley Cup playoffs.
On June 24, 2014, MacKinnon won the Calder Memorial Trophy for the rookie of the year, becoming the youngest player to ever win this trophy and third in Avalanche history behind Chris Drury and Gabriel Landeskog.
He was subsequently selected to the NHL All-Rookie Team.

MacKinnon recorded his first career NHL hat trick on February 22, 2015 in a 5–4 win over the Tampa Bay Lightning.
He is the youngest player in Avalanche history to record a hat trick.

On July 8, 2016, MacKinnon as a restricted free agent re-signed with the Avalanche, agreeing to a seven-year, $44.1 million contract that averages $6.3 million per season.
Later in the offseason, on October 13, 2016, MacKinnon was announced as an alternate captain for the Avalanche.

MacKinnon would play his first NHL All-Star Game on January 10, 2017, as the lone representative of the Colorado Avalanche.
He was again selected the following year for the 2018 NHL All-Star Game.

MacKinnon was named the NHL's First Star of the Week for February 26 through March 4, after scoring five goals, six assists, with four power play points, a +6 rating, and 31 shots in four games.
This included his second career five-point night (the previous being a goal and four assists against the Capitals earlier in the season, on November 16, 2017), with MacKinnon scoring two goals and adding three helpers in a 7–1 win over the Minnesota Wild on March 2.
On April 26, 2018, MacKinnon was nominated for the Ted Lindsay Award as the NHL's most outstanding player.
The following day he was named a Hart Memorial Trophy finalist as the NHL's most valuable player; the award was won by New Jersey Devils' forward Taylor Hall.
MacKinnon was signed to his first NHL contract, a three-year entry level deal, with the Avalanche on July 9, 2013. MacKinnon made his NHL debut to begin the 2013–14 season on October 2, 2013, becoming the youngest hockey player to ever dress in a regular season game for the Colorado Avalanche franchise, registering two assists in a 6–1 victory over the visiting Anaheim Ducks. MacKinnon scored his first NHL goal October 12, 2013, against Michal Neuvirth of the Washington Capitals during the second period at the Verizon Center.
During the season MacKinnon's role increased, as he was placed on the top two offensive lines. He claimed his first NHL record in becoming the youngest player to record back-to-back two-goal games from January 4–6, 2014, beating Dale Hawerchuk's of the original Winnipeg Jets from 1981. MacKinnon later compiled a 13-game point streak from January 25, to March 6, surpassing Wayne Gretzky (who turned 19 during his first season) to have the longest scoring streak by an 18-year-old in NHL history. MacKinnon finished the regular season appearing in all 82 games and led all rookies with 24 goals and 39 assists for 63 points. MacKinnon became just the third player in the NHL to record seven points in his first two playoff games with a goal and six assists in the first two contests against the Minnesota Wild in the opening round of the 2014 Stanley Cup playoffs. On June 24, 2014, MacKinnon won the Calder Memorial Trophy for the rookie of the year, becoming the youngest player to ever win this trophy and third in Avalanche history behind Chris Drury and Gabriel Landeskog. He was subsequently selected to the NHL All-Rookie Team.
MacKinnon recorded his first career NHL hat trick on February 22, 2015 in a 5–4 win over the Tampa Bay Lightning. He is the youngest player in Avalanche history to record a hat trick.
On July 8, 2016, MacKinnon as a restricted free agent re-signed with the Avalanche, agreeing to a seven-year, $44.1 million contract that averages $6.3 million per season. Later in the offseason, on October 13, 2016, MacKinnon was announced as an alternate captain for the Avalanche.
MacKinnon would play his first NHL All-Star Game on January 10, 2017, as the lone representative of the Colorado Avalanche. He was again selected the following year for the 2018 NHL All-Star Game.
MacKinnon was named the NHL's First Star of the Week for February 26 through March 4, after scoring five goals, six assists, with four power play points, a +6 rating, and 31 shots in four games. This included his second career five-point night (the previous being a goal and four assists against the Capitals earlier in the season, on November 16, 2017), with MacKinnon scoring two goals and adding three helpers in a 7–1 win over the Minnesota Wild on March 2. On April 26, 2018, MacKinnon was nominated for the Ted Lindsay Award as the NHL's most outstanding player. The following day he was named a Hart Memorial Trophy finalist as the NHL's most valuable player; the award was won by New Jersey Devils' forward Taylor Hall.
Nathan MacKinnon