Kerfoot was drafted as a youth in the 12th round, 254th overall, by the Western Hockey League 's Seattle Thunderbirds in the 2009 WHL Bantam Draft. A Vancouver native, Kerfoot opted to play as a midget with the Vancouver NorthWest Giants in the BC Hockey Major Midget League. In his second season with the Giants in 2011, Kerfoot led the team alongside Sam Reinhart to the championship. He led the BCMML with 72 assists and 108 points before earning MVP honours at the Telus Cup. He finished the 2010–11 season by joining the Coquitlam Express of the British Columbia Hockey League. On May 30, 2011, Kerfoot agreed to return to the Express for the 2011–12 season while completing his final year of high school at Collingwood. In the midst of the season, Kerfoot was selected to play for the Team Canada West squad at the World Junior A Challenge in Langley, British Columbia. He scored the winning goal in overtime to defeat Sweden in the semi-finals in which the team advanced to eventually win the gold medal. Kerfoot also enjoyed a standout season with the Express, placing third on the team after recording 25 goals and 44 assists in 51 games. He earned recognition in collecting the Coastal Rookie of the Year honours and a place in the All-Rookie Team and was announced in the First All-Star Team while winning the Bob Fenton Trophy as the BCHL's most sportsmanlike player. At the 2012 NHL Entry Draft, Kerfoot was selected by the New Jersey Devils in the fifth round, 150th overall. On August 20, 2012, Kerfoot announced his commitment to play NCAA hockey at Harvard University with the Crimson men's ice hockey team in the fall of 2013. Returning to the Express for his draft-plus-one year, Kerfoot appeared in just 16 games for the 2012–13 season before he was sidelined through injury. In beginning his collegiate career in the 2013–14 season, Kerfoot made his debut for Harvard and registered an assist in a 3–0 victory over Bentley University on October 26, 2013. He scored his first goal the next game in a 3–3 tie with Rensselaer Polytechnic Institute on October 29. In his freshman year, Kerfoot finished with 8 goals and 6 assists in 25 games. Kerfoot adjusted offensively in sophomore season, showing his playmaking ability to produce 30 points in 27 games. Alongside Jimmy Vesey and Kyle Criscuolo, Kerfoot solidified his breakout season in the following 2015–16 season in leading the Crimson with 30 assists as a junior. He was selected to the Second All-Ivy Team and earned a spot in the ECAC Third All-Star Team. In his senior season, with the departure of his linemates Vesey and Criscuolo, Kerfoot was announced as team co-captain of the Crimson for the 2016–17 season. Kerfoot flourished in his senior year, helping take the Crimson to the Frozen Fourfor the first time since 1994. In co-leading the team with 45 points in 36 games, he received the John Tudor Memorial Cup as Harvard's MVP, earning ECAC First Team honours and was named as a top-ten finalist for the Hobey Baker Award as the top men's ice hockey player in the NCAA. He completed his career with the Crimson with 123 points in 121 games.
Professional
Having completed his four-year collegiate career, Kerfoot chose not to sign a contract with the NHL organization that drafted him, the New Jersey Devils, rendering him a free agent. Having rejected the Devils due to their prospect depth at the centre position, Kerfoot received NHL-wide interest including from his hometown club, the Vancouver Canucks. However, on August 23, 2017, Kerfoot signed a two-year, entry-level contract with the Colorado Avalanche. After an impressive training camp with the Avalanche, Kerfoot played in a scoring-line role throughout the pre-season and secured a spot on the opening roster for the 2017–18 season. He made his NHL debut with the Avalanche, playing on a line with Matt Duchene and Nail Yakupov. He registered his first NHL point with an assist on Tyson Barrie's game-winning goal in a 4–2 victory over the New York Rangers at Madison Square Garden on October 5, 2017. He scored his first NHL goal on October 11 against the Boston Bruins in the Avalanche's season home opener. On July 1, 2019, Kerfoot was traded to the Toronto Maple Leafs in exchange for Nazem Kadri, Calle Rosén and a third-round pick in 2020. On July 4, as a restricted free agent, Kerfoot signed a four-year, $14 million contract with the Maple Leafs worth an average annual value of $3.5 million.
Personal
Kerfoot's father, Greg Kerfoot, is the majority owner of Vancouver Whitecaps FC of Major League Soccer. Alexander majored in economics while at Harvard. He is the older brother to Colton and Daniel, both of whom also play hockey—Colton mirrored Alexander's path in committing to Harvard and played his freshman season as Alexander captained the Crimson in his final year in 2016–17.
