[8] Mitchell was born and raised in Port McNeill, British Columbia, a small logging town on Vancouver Island.

[5] He played minor hockey as a winger with the North Island Eagles and won back-to-back double-A provincial titles in pee wee and bantam with the club.

[4] At the age of 15, he left home after being recruited to play for Athol Murray College of Notre Dame, a high school in Wilcox, Saskatchewan.

He returned to Melfort for a second season and recorded 56 points in 64 games to earn the Top Defenceman Award and SJHL First All-Star Team honours.

[15] As Clarkson met Princeton in the 1999 ECAC Semi-final, Mitchell scored the game winning goal with a slap shot from centre ice with three seconds remaining in regulation.

[14] He played the final six games of the 1998–99 AHL season with the Devils' minor league affiliate, the Albany River Rats, registering a goal and three assists.

In his first Devils' training camp in September 1999, he broke a finger in his left hand during a fight in a rookie game against the Boston Bruins.

Mitchell received a call-up late in the season and made his NHL debut on March 27, 2000, in a 5–2 loss to the Toronto Maple Leafs.

[28] He suffered a cheekbone injury during the first round against the Colorado Avalanche that required him to wear a fully visored helmet for the remainder of the playoffs.

[36] In December 2005, he was named team captain as part of the Wild's monthly rotating captaincy (he was then succeeded by Brian Rolston in February 2006).

[38] Mitchell closed the season playing 16 games and one playoff round with Dallas before becoming an unrestricted free agent in the off-season.

[39] His acquisition as a free agent followed the signings of goaltender Roberto Luongo and head coach Alain Vigneault, which reflected an effort from Nonis to develop a defence-first system.

[7] With the departure of long-time Canucks captain Markus Näslund to free agency in the 2008 off-season, Mitchell was considered a leading candidate for captaincy.

[46] Due to Luongo's limitations as a goaltender, Mitchell was designated the captain's traditional role of disputing calls by the officials and relaying messages to the coach.

[46] During the subsequent 2008–09 season, Mitchell recorded career-highs with three goals, 20 assists, 23 points and a team-best +29 rating,[47] earning his second consecutive Babe Pratt Trophy.

[50] Early on in the 2009–10 season, Mitchell delivered an open-ice hit that concussed Blackhawks captain Jonathan Toews in the two teams' first game against each other since the 2009 playoffs.

"[56] Not speaking to the media until after the Canucks were eliminated in the playoffs, he expressed criticism towards both Malkin for the hit resulting in his concussion and to NHL Senior Vice President Colin Campbell for not taking any disciplinary action.

He denounced Campbell for being "inconsistent...hand[ing] down suspensions and fines on result [instead of the nature of a hit]," as Mitchell's injury was not immediately apparent following the game.

Mitchell was still involved in negotiations with Vancouver to re-sign, but concerns over his head injury, as well as the new defensive acquisitions of Keith Ballard and Dan Hamhuis in the off-season factored against the possibility of remaining with the Canucks.

[60] Nearly a month into the campaign, he notched his first goal as a King, scoring short handed against the Dallas Stars in a 5–2 victory on October 28, 2010.

[56] Later in the season, during a game against the Phoenix Coyotes, on March 3, 2011, Mitchell was hit in the face by a shot from opposing forward Kyle Turris, requiring 53 stitches.

In the 2012 playoffs, Mitchell helped the Kings defeat the Vancouver Canucks in the first round, the St. Louis Blues in the semi-finals (winning four games straight) and the Phoenix Coyotes in the Conference Finals.

[64] Mitchell missed the final 42 games of the 2015–16 NHL season largely over concern what another brain injury would mean to his long-term health.

After the Minnesota Wild failed to qualify for the 2004 playoffs, he was named to the national team for the 2004 World Championships in the Czech Republic.

[nb 1] He was joined on the squad by Wild teammate Nick Schultz in the first group of players chosen by General Manager Jim Nill on April 5, 2004.

[68] While with the Vancouver Canucks, he established himself as their top shutdown defenceman, being matched up against opposing teams' best players and spending significant time on the penalty kill.

[72] Prior to a game against the Calgary Flames on February 17, 2009, opposing head coach Mike Keenan accused Mitchell of playing with an illegal hockey stick.

[4] They reside in the Yaletown neighbourhood in downtown Vancouver,[5] while returning to Mitchell's hometown of Port McNeill during the summer, where he fishes avidly.

In 2004, he hosted the first Willie Mitchell Classic, a celebrity golf tournament to raise scholarship funds for high school students around his hometown.

On September 14, 2022, the Tofino Resort and Marina, co-owned by Mitchell, announced the cancellation of their Race for the Blue fishing tournament and temporary closure of the 1909 Kitchen and Bar as a result of allegations of inappropriate behavior by members of staff.