[1] Horton grew up in Dunnville, Ontario, playing much of his minor hockey with the Welland Tigers of the OMHA South Central AAA League until his Minor Peewee year before making the move to play in the Greater Toronto Hockey League with the Toronto Red Wings.

Entering his peewee season, he left the Red Wings to go play for the Thorold Blackhawks Jr. B. club of the Ontario Hockey Association (OHA)'s Golden Horseshoe League at age 13.

[6] Horton was named to the Canadian national junior team's selection camp in December but was one of the first cuts.

[5] In January 2002, Horton, along with Patrick O'Sullivan and Kevin Klein, was regarded as a top prospect from the OHL for the 2003 NHL Entry Draft.

[9] Midway through the 2002–03 season, Horton was regarded as a top-five North American prospect by the NHL Central Scouting Bureau.

[14] After his signing, Panthers head coach Mike Keenan compared Horton to future New York Rangers Hall of Famer Mark Messier.

[15] Against the Minnesota Wild on October 24, Horton recorded his first career point with an assist on an Ivan Novoseltsev goal.

[18] On January 9, 2004, Horton became the first rookie in NHL history to record a goal on a penalty shot, scoring against Philadelphia Flyers goaltender Jeff Hackett.

[20] Four days after his penalty shot goal, Horton suffered a torn rotator cuff and labrum which could potentially have ended his season.

[23] Following an examination by surgeon Tony Miniaci, Horton was told he could rehabilitate naturally and did not require surgery on his shoulder.

[31] For the second straight season, the Panthers did not allow Horton to play for the Canadian national junior team.

[41] Against the Nashville Predators on December 13, Horton recorded his first career hat-trick and stated after the game: "It's a pretty nice feeling.

[61] Through seven games for the Panthers to open the 2007–08 NHL season, Horton recorded three goals and three assists, during which he had a four-game point streak.

[63] Against the Washington Capitals on November 28, Horton, along with teammates Olli Jokinen, Kamil Kreps and Stephen Weiss, scored shootout goals to help Florida win the game.

[64] For the first time since March 2007, Horton scored two goals in a game to help the Panthers win over the Atlanta Thrashers on December 28.

[69] Horton scored a goal against the Washington Capitals to help Florida win 4–2 in the game after Richard Zedník suffered a neck injury in which he had his external carotid artery cut by a skate.

[70] Twenty-two seconds into overtime against the Boston Bruins on March 5, Horton scored to give the Panthers a 1–0 victory.

There's a group of guys underneath him that I think can make a lot bigger jumps than I need out of Nathan Horton goal-wise.

"[75] Against the Nashville Predators on November 1, Horton played in his 300th career game, but failed to record a point.

[81] In early March, days after the trade deadline, Horton suffered a finger injury that forced him to have surgery.

[86] In game three of the 2011 Stanley Cup Finals, Horton was seriously injured on a late hit by Vancouver Canucks defenceman Aaron Rome.

This was arguably the turning point in the series, as the Bruins would go on to win four of the next five games and score 21 of the next 25 goals against the Presidents' Trophy-winning Canucks after the hit.

[88] Although Horton missed the remainder of the finals, he was able to hoist the Stanley Cup in Vancouver on June 15 after the Bruins won Game 7.

Horton did not play for another team during the 2012–13 NHL lockout and made his 2013 season debut for the Bruins on January 19, 2013, opening night against the New York Rangers.

On the day of the 2013 NHL Entry Draft, Horton's representatives confirmed he had informed Bruins general manager Peter Chiarelli he would not be re-signing with Boston.

[89] On July 5, 2013, Horton signed a seven-year free agent contract worth $37.1 million with the Columbus Blue Jackets.

[90] However, off-season shoulder surgery would sideline Horton until January 2, 2014, when he finally made his Blue Jackets debut and scored the game-winning goal in a 2–0 victory over the Phoenix Coyotes.

[91] During the first period of a March 10, 2014 game against the Dallas Stars, Horton scored a goal to put the Blue Jackets ahead, 1–0.

Shortly thereafter, Dallas Stars center (and Horton's former Bruins teammate) Rich Peverley collapsed on the bench.

[94] On February 26, 2015, with Horton on the long-term injured list and with no sign of return, he was traded due to financial considerations by the Blue Jackets to the Toronto Maple Leafs in exchange for David Clarkson.