Nash, Andrew Murray, and Fedor Tyutin each scored in the third period, and the Blue Jackets tallied five unanswered goals to beat the Blues 5-2 on Saturday night.
Columbus, which came back from a 2-0, first-period deficit, has earned at least a point in five straight games.
St. Louis has lost three of four.
Columbus had won just one time in 11 previous trips to St. Louis.
"This has been a real tough place for us to play - no success here at all," said Nash. "We knew we had to do something to change things around."
The Blue Jackets' last regulation win in St. Louis was a 4-1 victory on March 27, 2007.
Columbus used some early physical play to help set the tone. The Blue Jackets engaged in two fights in the first 2:28. Derek Dorsett battled St. Louis winger Brad Winchester just 10 seconds into the game. Enforcer Jared Boll, who scored the tying goal midway through the second period, fought with B.J. Crombeen just over two minutes later.
"It was a little frustrating when you come in here and lose this many times," said Boll. "We were sick of it."
Antoine Vermette got the Columbus rally started with a first-period goal.
"It seems like we're more effective when we tend to be more physical," Vermette said.
Columbus scored three goals in the third period, including two in the final 3:28. Andrew Murray broke a 2-2 tie by deflecting in a shot from the blue line by Jan Hedja at 3:40. It was his third goal of the season and first since Dec. 27. Nash added a power-play score at 16:32 to give him a team-leading 22 goals this season. Tyutin scored an empty netter at 18:30.
"I thought we managed the game pretty well," said Columbus coach Scott Arniel. "We just kept going and really took over in the second period. It carried through the rest of the game. A real strong 60 minutes."
Columbus, which beat Florida 3-2 on Wednesday, won back-to-back road games for the first time since Nov. 19-20.
"We're starting to play better, to get things going," said Nash. "To come in here and get two points against a team we're going to battle for a playoff spot - that's huge."
Eric Brewer and Patrik Berglund scored in a span of 1:23 in the first period to give St. Louis a 2-0 lead. Alex Steen assisted on both goals, giving him a career-best seven-game point streak. Berglund's goal was his 11th of the season and third in as many games.
Vermette and Boll then answered for Columbus. Boll scored his fifth goal of the season on a breakaway in the second period.
Columbus outshot St. Louis 14-5 in the second period. The Blues' first shot came 12:12 into the period.
"We came out and established our game," said St. Louis coach Davis Payne. "Then all of a sudden we decided to re-define ourselves. We were never able to stop the downhill slide."
Steve Mason stopped 19 shots to improve to 15-11-2. He gave up two goals on the first six shots before rebounding to close the game with 15 straight saves.
"It was up to me to shut the door the rest of the way," said Mason.
Columbus held St. Louis without a shot for a stretch of 15:57 in the first and second periods.
"It was a lack of attention to detail," added Payne. "Inexcusable."
Derick Brassard and Jakub Voracek each assisted on the last two Columbus goals.
Notes: Blue Jackets D Rostislav Klesla was helped off the ice in the third period with a knee injury. He did not return. .. The Blues are tied with Anaheim for first in the NHL with 48 fighting majors. ... St. Louis Rams coach Steve Spagnuolo was in attendance. ... Blues D Barret Jackman missed the game with a lower-body injury. He is listed as day-to-day. Jackman missed nine games earlier in the season with a knee injury. ... The Blue Jackets' previous five games were decided by one goal. ... Mason is 6-2-1 in his last nine games.
|Eric Brewer (7) ASST: Alexander Steen (20), Brad Boyes (17)|
1 - 0 STL
|PPG - Patrik Berglund (11) ASST: Alexander Steen (21), Alex Pietrangelo (18)|
2 - 0 STL
|Antoine Vermette (11) ASST: R.J. Umberger (16), Kristian Huselius (6)|
2 - 1 STL
|Jared Boll (5) ASST: Derek MacKenzie (4), Matt Calvert (1)|
2 - 2 Tie
|Andrew Murray (3) ASST: Jan Hejda (7), Samuel Pahlsson (7)|
3 - 2 CBJ
|PPG - Rick Nash (22) ASST: Derick Brassard (20), Jakub Voracek (21)|
4 - 2 CBJ
|EN - Fedor Tyutin (5) ASST: Derick Brassard (21), Jakub Voracek (22)|
5 - 2 CBJ
|Power Play %||21.7%||22.3%|
|% on Road||21.5%||25.4%|
|% at Home||22.0%||19.4%|
|Brad Winchester Fighting (maj) against Derek Dorsett|
|Derek Dorsett Fighting (maj) against Brad Winchester|
|B.J. Crombeen Fighting (maj) against Jared Boll|
|Jared Boll Fighting (maj) against B.J. Crombeen|
|Derek Dorsett Interference against Brad Winchester|
|Jay McClement Delaying Game-Puck over glass|
|Marc Methot Fighting (maj) against Tyson Strachan|
|Tyson Strachan Fighting (maj) against Marc Methot|
|Roman Polak Interference against Jakub Voracek|
|Fedor Tyutin Hooking against Alexander Steen|
|Grant Clitsome Tripping against T.J. Oshie|
|David Backes Interference against Rostislav Klesla|
|Ian Cole Hooking against R.J. Umberger|
|Erik Johnson Misconduct (10 min)|
|Ryan Reaves Roughing against Marc Methot|
|Jan Hejda Roughing against Erik Johnson|
|Marc Methot Roughing against Ryan Reaves|
|Erik Johnson Roughing against Jan Hejda|
|Erik Johnson Roughing against Jan Hejda|