Not long after being drafted, Downie was suspended for five games early in the 2005–06 OHL season for an on-ice altercation with teammate Akim Aliu.

During a practice on September 28, 2005, Downie cross-checked Aliu in the face without warning, knocking out seven of his teeth, and then proceeded to fight his younger teammate.

Aliu described other hazing incidents leading to the attack and stated he viewed them as being racially motivated, calling Downie a "racist sociopath" and further remarking "He looked at me and saw a black boy with a weird accent — and didn’t like me because of it.

"[7] After attending Flyers' training camp in the Fall and playing in several pre-season games, however, the club returned Downie to Peterborough.

Downie returned to the international stage yet again in December 2006, participating in the 2007 World Junior Ice Hockey Championships in Leksand and Mora, Sweden.

[11] After serving his suspension in the AHL, Downie made his long-awaited NHL regular season debut with the Flyers on December 5, 2007, against the Minnesota Wild.

During the 2008 Stanley Cup playoffs, in Game 3 of the Eastern Conference Finals on May 13, 2008, Downie hit Petr Sýkora as the play ended on Ryan Malone's goal that gave the Pittsburgh Penguins a 3–1 lead.

On November 7, 2008, Downie was traded by the Flyers to the Tampa Bay Lightning, along with Steve Eminger, in exchange for defenceman Matt Carle.

Downie was immediately assigned to Tampa Bay's AHL affiliate, the Norfolk Admirals, before he was recalled and made his Lightning debut in a 4–2 defeat against the Minnesota Wild on November 28, 2008.

[14] Downie continued to split the season between Norfolk and Tampa Bay, and his reputation for unnecessary aggressive behaviour was further developed on February 28, 2009, after he slashed a linesman, Mike Hamilton, in the shin following a controversial empty-net goal in a game against the Hershey Bears, receiving a game misconduct for physical abuse of an official.

In contributing to the Lightning's return to the Stanley Cup playoffs in 2011, Downie led the team in plus-minus rating and finished fourth in team scoring with 14 points, as the Lightning ultimately reached the Eastern Conference Finals, falling to the eventual Stanley Cup champions, the Boston Bruins.

[21] He later set a Lightning franchise record for two quickest goals by an individual when he scored twice within the span of 11 seconds against Pittsburgh on February 12, 2012.

[25] Downie continued to score 13 points in 20 games whilst hampered by a lingering shoulder injury as the Avalanche failed to qualify for the 2012 playoffs.

[27] Having used the NHL lock-out to recuperate from off-season surgery, Downie entered the shortened 2012–13 season in full health, only to suffer a season-ending knee injury in just his second game of the campaign; he was injured trying to hit Davis Drewiske of the Los Angeles Kings, requiring surgery to repair a torn anterior cruciate ligament (ACL) in his right knee.

[28] On October 31, 2013, after producing seven points in 11 games with the Avalanche to start the 2013–14 season, Downie was traded back to the Philadelphia Flyers in exchange for Maxime Talbot.