Ben Bishop allowed one goal on 20 shots after relieving Ty Conklin midway through the first period with St. Louis trailing 3-1.
The Blues scored three times on four shots against Steve Mason in the shootout with Alex Steen getting the deciding tally.
The Blues honored four players who starred for the franchise wearing No. 7 in a pre-game ceremony for the 34th straight home sellout, also one of the more enthusiastic crowds for a matchup of teams on the outside of the playoff hunt.
St. Louis won for only the second time in nine games and avoiding dropping below .500 for the first time all season, and sent the Blue Jackets to their fifth straight loss.
Jakub Voracek had a goal and assist for Columbus, and Rick Nash had two assists.
Patrik Berglund added a goal and an assist for the Blues, who totaled four goals the previous four games. David Backes had two assists, ending a five-game point drought.
The game settled down considerably after a wide-open first period that featured two fights in the first two minutes. Conklin was yanked after allowing three goals on eight shots, by Voracek, Matt Calvert and Fedor Tyutin, and with St. Louis trailing 3-1 midway through the period.
McDonald and T.J. Oshie scored power-play goals in a span of 1:15 to tie it and Columbus didn't get off a shot against Bishop the rest of the period.
The Blues made it three in a row on McDonald's second of the game and 16th overall at 6:53 of the third when he doubled back on a wraparound and tucked the puck in. Derek MacKenzie nudged the puck over the line on Nash's backhand on a 2-on-1 break to tie it at 10:28.
Notes: The Blues entered the game with 62 fighting majors, second-most in the NHL. Forward Chris Stewart played to the crowd, waving his arms, after getting the better of Derek Dorsett. ... Tyutin had been scoreless the previous five games and Calvert the previous three. ... St. Louis goalie Jaroslav Halak faced shots in the pre-game skate and could return from a fractured hand that has sidelined him for 11 games on Wednesday in Columbus.