MacKinnon's two first-period goals staked the Avs to a 2-0 lead, and the Blues never managed to equalize. He added an assist to extend his points streak to 10 games and now has 10 goals and 10 assists during the stretch.
Rantanen scored his second goal in the game's final minute to cap a four-point night as he also recorded two assists.
Avs captain Gabriel Landeskog chipped in three assists.
Joel Edmundson, in his first game back since missing five weeks with a fractured forearm suffered against Colorado on Feb. 8, scored the Blues' lone goal.
The Avalanche posted their sixth win in nine games while grabbing the top wild-card spot in the Western Conference ahead of Dallas, and moving within a point of third-place Minnesota in the Central Division playoff race.
The slumping Blues, who have plummeted in the standings since November, suffered their third straight loss and eighth in the past 11 games.
MacKinnon scored his goals less than three minutes apart in the first period. The first goal came on a three-way passing play that he began and finished midway through the first period. Rantanen and Landeskog earned assists on the goal.
Just under three minutes later, MacKinnon added his second, knocking in Tyson Barrie's rebound.
Edmundson snapped home a shot from the blue line at 9:15 of the second period, bringing the Blues within a goal at 2-1.
But Rantanen restored Colorado's two-goal lead at 16:29 of the second period as he took Landeskog's pass from the Avalanche end. Skating near the St. Louis blue line, Rantanen accepted a pass and then scored on a partial breakaway, beating Allen with a backhand.
Avs goalie Semyon Varlamov stopped 44 of 45 shots for his 20th win of the season - while making his 15th straight appearance.
St. Louis goal Jake Allen stopped 19 of 22 shots.
--Field Level Media
Colorado | St. Louis | |
Mikko Rantanen 4 | Points | Joel Edmundson 1 |
Mikko Rantanen 2 | Goals | Joel Edmundson 1 |
Gabriel Landeskog 3 | Assists | Dmitrij Jaskin 1 |
N/A | Power Play Goals | N/A |
N/A | Short Handed Goals | N/A |
Semyon Varlamov .978 | Save Percentage | Jake Allen .864 |
Semyon Varlamov 44 | Saves | Jake Allen 19 |
Team | Shots | Goals | Power Play | Penalty Kill | Penalty Mins | Face Offs Won |
Colorado | 23 | 4 | 0-1 | 2-2 | 4 | 21 |
St. Louis | 45 | 1 | 0-2 | 1-1 | 2 | 23 |