After beginning his major junior career at the early age of 15 in the Ontario Hockey League (OHL), Spezza was selected second overall in the 2001 NHL Entry Draft by the Ottawa Senators, eventually serving as their team captain following the departure of Daniel Alfredsson.

Following his retirement, he spent a year in the Maple Leafs' front office, before taking his current role with the Penguins.

The victory resulted in Spezza becoming the poster boy for Baby, a Broadway musical that played at Toronto's O'Keefe Centre in the summer of 1984.

[4] At age 15, Spezza began his major junior career in the Ontario Hockey League (OHL) with the Brampton Battalion in 1998–99, under a rule permitting the then-underage player to play on his hometown team.

The second overall pick originally belonged to the New York Islanders but was traded to Ottawa (along with Zdeno Chára and Bill Muckalt) in exchange for Alexei Yashin on the day of the Draft.

However, the Senators failed to advance past the first round following their Stanley Cup run the previous season, falling to the Pittsburgh Penguins in four games.

[18] However, Spezza's poor defensive play and costly turnovers in that series resulted in him being booed by fans at Scotiabank Place, and the following off-season was rife with speculation that he would be traded.

Letang received a two-minute penalty for boarding and Spezza was expected to miss four-to-six weeks due to a consequent shoulder injury.

[21] At the end of the 2010–11 season, Spezza was named an interim alternate captain for Ottawa after the team traded away Mike Fisher.

[24] Spezza spent time with Rapperswil-Jona Lakers of the Swiss National League A during the 2012–13 NHL lockout and returned to the Senators once a resolution had been negotiated.

The Senators announced on January 31, 2013, that Spezza would be out of the Ottawa line-up for a minimum of two months (and possibly longer) as he required surgery for a herniated disc in his back.

[26] On September 14, 2013, Spezza was named the eighth captain in Senators' franchise history, replacing long-time teammate Daniel Alfredsson, who joined the Detroit Red Wings as a free agent on July 5, 2013.

His offensive production improved the following season, scoring 33 goals, 30 assist and 63 points in 75 games as the Stars qualified for the 2016 playoffs as the top seed in the Western Conference.

[34] He finished the 2018-19 NHL season with 8 goals, 18 assists and 27 points in 76 games and the Stars got back into a playoff spot for the first time in 3 years.

On July 1, 2019, as a free agent, Spezza signed a one-year, $700,000 contract for the 2019–20 season with the Toronto Maple Leafs,[35] the team he supported as a child.

[40] Two and a half weeks later, Spezza would go on to record his eighth and final career hat trick in a 7–3 victory over the Vancouver Canucks on February 4.

Spezza's deal was seen as another hometown discount for the salary cap strapped club, stating "if I could take less, I would" to help the team win.

[44] Following the Leafs' elimination in the first round of the 2022 Stanley Cup playoffs by the Tampa Bay Lightning, Spezza announced his retirement after 19 seasons in the NHL.

"[45] Spezza's loyalty to his hometown Maple Leafs factored into his decision, stating that he believed that it was best for the on-ice product for him to retire and open opportunity for young offensive players.

Spezza made it to the gold medal game with Canada in his third and final World Junior appearance in 2002, but lost to Russia to earn the silver.

He would make his men's debut for Canada at the 2008 World Championships, being named to the team along with Senators linemate Dany Heatley.

Spezza, along with Finland's Niko Kapanen and fellow Canadian Steven Stamkos, finished the tournament tied for first in goals scored with seven.

However, after veteran Joe Sakic announced his retirement and Ryan Getzlaf declared that he required more time to recover from injury, Spezza was invited to fill in one of the vacant spots.

[50] As the 2012–13 NHL lockout continued, Spezza was named to Canada's roster for the 2012 Spengler Cup held in Davos, Switzerland.

Spezza joined fellow NHL stars John Tavares, Tyler Seguin, Patrice Bergeron, Ryan Smyth, and Matt Duchene in the Canadian line-up,[51] helping Canada defeat host team HC Davos to capture its first Spengler Cup title since 2007.

[52] At the 2015 World Championships, where Canada won the gold medal for the first time since 2007 with a perfect 10–0 record, Spezza was named best forward and a member of the all-star team; he was the tournament's leading scorer.

[53][54] For the 2022–23 Toronto Maple Leafs season, Spezza was hired as special assistant to the general manager, Kyle Dubas.

The ceremony took place at Notre Dame Cathedral Basilica and the reception was held across the street at the National Gallery of Canada.

[64] Spezza's younger brother Matthew was a goaltender who last played for the Flint Generals of the International Hockey League (IHL).