During the 2012–13 NHL lockout, Seguin played for EHC Biel of the Swiss National League A (NLA) and finished the season with 25 goals, the most on the team.

[7] He had his sights set on playing hockey at the University of Michigan, and believed that St. Michael's would be a good stepping stone towards that goal.

[11] He finished the season with 106 points (48 goals and 58 assists) in 63 games, and, although the Whalers were swept in the second round of the 2010 playoffs, Seguin became the first member of the team to win the Red Tilson Trophy for most outstanding player in the OHL since David Legwand in 1998.

[12] He also tied with Taylor Hall of the Windsor Spitfires for that year's Eddie Powers Memorial Trophy, given to the top scorer in the OHL.

Both players were tied for points scoring in the OHL for the previous season, while draft reports tended to emphasize Seguin's speed and Hall's strength.

[15] Danny Flynn of Bleacher Report referred to Seguin as an "elite playmaker" who lacked "skill on the defensive end", whereas Hall had proven his "greatness on the big stage", but had "shown a tendency to be selfish at times".

Late in the 2010–11 season, Seguin was quoted as having a desire to model his NHL playing style on that of teammate Patrice Bergeron.

On June 15, 2011, Boston game seven of the Finals, earning the Stanley Cup with a 4–3 series victory over the Presidents' Trophy-winning Vancouver Canucks.

On November 5, 2011, Seguin scored his first career NHL hat trick against the team that traded the draft pick to the Bruins, the Toronto Maple Leafs.

[24] He made his Swiss League debut on September 30, centreing Ahren Spylo and Eric Beaudoin on the second line and scoring an assist in a 6–3 loss to the Rapperswil-Jona Lakers.

[27] On December 28, Seguin told NBC Sports Boston that, after representing Team Canada at the 2012 Spengler Cup, he would leave EHC Biel and return to the Bruins.

His performance began to waver during the 2013 playoffs, however, scoring only one goal and three assists in his first 12 postseason games, and he was moved from the second to the third line with Rich Peverley and Chris Kelly, with Jaromír Jágr taking his place on the first and/or second.

[32] On July 4, 2013, just 10 days after the Bruins game six loss in the Stanley Cup Finals, Seguin was part of a massive seven-player trade that sent him, Peverley, and defenceman Ryan Button to the Dallas Stars in exchange for forward Loui Eriksson and prospects Joe Morrow, Reilly Smith, and Matt Fraser.

[33] Prior to the trade, rumors had begun to circulate that the Bruins were displeased with Seguin's supposed hard-partying lifestyle, particularly when his on-ice performance began to suffer during the playoffs.

[34] General manager Peter Chiarelli spoke in a press conference on July 4 to assert that, although the trade was "not a strict on-ice decision", but that concerns of Seguin's behavior were more related to "focus, just about little things, about preparing to play, it was nothing about extracurricular activities".

[39] He was also nominated for the King Clancy Memorial Trophy, given for leadership and humanitarianism;[40] the award ultimately went to Edmonton Oilers defenceman and ex-Bruins teammate Andrew Ference.

At the end of the 2017–18 season, Seguin was nominated by the Stars for the King Clancy Memorial Trophy for the second time but was not named a top three finalist in the league.

After blocking a shot on March 12, 2020, one of the final games before the cancelation of the last three weeks of the 2019–20 season due to the COVID-19 pandemic protocols, Seguin suffered two tears in his right vastus lateralis muscle.

On July 29, during a practice before the Stars' exhibition game against the Nashville Predators, Seguin felt a "pop" in his hip that also caused pain in his knee.

[51] Seguin was activated from the injured reserve on May 3, 2021 making his debut that day and scoring a goal in the Stars' 5–4 overtime loss against Spencer Knight of the Florida Panthers.

[53] After playing 19 of the first 24 games of the 2024–25 season and recording nine goals and 11 assists for 20 points, it was announced on December 4, 2024, that Seguin would undergo hip surgery to repair a femoral acetabular infringement and labrum, taking him out of the Stars line-up for four-to-six months.

[60] Previously, he won gold with Team Ontario in the 2009 World U-17 Hockey Challenge in Port Alberni, British Columbia,[61] and finished second in tournament scoring with 11 points in six games.

At every Stars home game during the season, Seguin donated a luxury suite, along with food and beverage, for individuals with spinal cord injuries.

[74] At the conclusion of every game, Seguin meets his special guests outside of the Stars' locker room for autographs and pictures, often with other members of the team.