Toffoli was chosen by the Los Angeles Kings in the second round (No. 47) of the 2010 NHL Draft. By his third full NHL season (2015-16), he led them in goals (31).

Toffoli began the 2013-14 season with Manchester in the American Hockey League, then started his full NHL season with a five-game point streak, including his first two-goal game in a 5-1 win against the Vancouver Canucks on Nov. 9, 2013. He finished 2013-14 tied for the lead among first-year players with five game-winning goals, fourth among rookies at plus-21 and tied for 12th in rookie scoring with 29 points (12 goals, 17 assists).

The native of Scarborough, Ontario has a quick and accurate shot, above-average speed and good hockey sense. After making his NHL debut against the San Jose Sharks on March 16, 2013, Toffoli scored his first NHL goal and assist two days later in the Kings' 4-0 victory against the Phoenix Coyotes. He made his Stanley Cup Playoff debut that season, in Game 5 of the first round against the St. Louis Blues.

Toffoli scored his first NHL playoff point when he assisted on a late game-winning goal in Game 2 of the Western Conference Semifinals against San Jose and scored his first NHL playoff goal in Game 3. After scoring one goal and four points in four games of the Western Conference Final against the Chicago Blackhawks, Toffoli finished the playoffs tied for first among rookies with six points. His seven goals and 14 points in the postseason ranked first among NHL rookies. He also set team records by a Kings rookie in the playoffs and helped Los Angeles win the Stanley Cup.

The forward led the Kings at plus-25 in 2014-15, set a team record by scoring four shorthanded goals in his first 18 games and led the NHL with five shorthanded goals. On Feb. 12, 2015, Toffoli got his first career hat trick and added an assist to help the Kings defeat the Calgary Flames 5-3.

Toffoli became the first player in NHL history to score a hat trick in an outdoor game when Los Angeles defeated the Colorado Avalanche 3-1 in the 2020 Navy Federal Credit Union NHL Stadium Series at Falcon Stadium, U.S. Air Force Academy in Colorado Springs, Colorado. Two days later, he was traded to the Canucks on Feb. 17, 2020. Two days later, he was traded to the Vancouver Canucks and then signed a four-year contract with the Montreal Canadiens on Oct. 12, 2020, but was traded to the Calgary Flames on Feb. 14, 2022, reuniting him with Darryl Sutter, his coach in Los Angeles.

Toffoli got his 200th NHL goal in his 672nd NHL game, a 3-2 Flames loss to the Carolina Hurricanes on Nov. 26, 2022. He finished the 2022-23 season with Flames highs in goals (34) and points (73) in 82 games and was named captain for Canada at the 2023 IIHF World Championship.

Toffoli was traded to the New Jersey Devils on June 27, 2023, for Yegor Sharangovich and a third-round pick in the 2023 NHL Draft. He had 44 points (26 goals, 18 assists) in 44 games before he was traded to the Winnipeg Jets on March 8, 2024, for two draft picks.

He signed a four-year, $24 million contract with the San Jose Sharks on July 1, 2024.