He played for fifteen seasons in the National Hockey League (NHL) as a member of the St. Louis Blues, Boston Bruins and Anaheim Ducks.

Forgoing his senior year with the Mavericks, he turned professional with the Blues, joining their American Hockey League (AHL) affiliate, the Peoria Rivermen.

[1] After spending parts of two years in junior hockey with the Lincoln Stars of the USHL, Backes was selected in the second round, 62nd overall, by the St. Louis Blues in the 2003 NHL Entry Draft.

Forty-four seconds into the game, Backes registered his first NHL point, a second-assist on a Doug Weight goal, giving the Blues a 1–0 lead.

[3] The following game, two days later, Backes scored his first NHL goal 10 minutes and 47 seconds into the first period versus the Los Angeles Kings.

Becoming a restricted free agent in the off-season, Backes signed a three-year, US$7.5 million offer sheet with the Vancouver Canucks on July 1, 2008.

[6] With a new contract, Backes tallied 54 points, including a career-high 31 goals, in 2008–09, finishing second behind former Bruins winger Brad Boyes among Blues scorers.

Backes completed the season matching his personal best total of 31 goals, while adding 31 assists for a career-high and team-leading 62 points over 82 games.

Late in the 2010–11 season, Blues captain Eric Brewer had been traded away to the Tampa Bay Lightning, leaving the leadership position vacant for the remainder of the campaign.

However, a re-evaluation shortly thereafter, with Backes' most recent game on October 30, on the road against the Columbus Blue Jackets, revealed that an operation to remove part of his colon would be necessary; it was carried out on November 2, with a projected eight-week recovery time.

[16] Following an accidental hockey-skate cut above one knee suffered in a March 17, 2018 Bruins road game by the Tampa Bay Lightning's Yanni Gourde,[17] Backes required 17 stitches to close the wound, and needed to stay off the ice for it to heal - Backes returned against the Lightning in a home game for the Bruins on March 29.

[18] Ahead of his return on March 29, Backes was selected as the Bruins' nominee for the Bill Masterton Trophy, which is awarded to the player who "best exemplifies the qualities of perseverance, sportsmanship and dedication to hockey.

On February 21, 2020, the Bruins traded Backes, prospect Axel Andersson and a 2020 first-round pick to the Anaheim Ducks in exchange for Ondřej Kaše.

He again suited up for Team USA at the 2008 IIHF World Championship,[24] contributing an assist and 35 penalty minutes over six games as the U.S. finished sixth.

[28] Although the U.S. team did not win a medal, the forward played in six games, scored three goals, had one assist, and four points — while accumulating six penalty minutes — in Sochi.

[32] In November 2013, they founded Athletes for Animals, an organization to raise funds and awareness for rescuing and protecting the welfare of homeless pets.

[33] On April 4, 2017, six cattle that escaped slaughter in north St. Louis were put under the care of The Gentle Barn, an animal sanctuary with facilities in California and Tennessee with David and Kelly helping provide support to the community based GoFundMe campaigns created for their freedom.