Cristian Fernando Osorio's 81st-minute goal was enough to give Once Caldas a 1-0 victory at home to Deportivo Pasto on Sunday.
It was also enough for Once Caldas to move top of the table after Santa Fe were beaten 1-0 by in-form Atletico Nacional, while Medellin slumped to a 2-1 loss to Alianza Petrolera.
Once Caldas now enjoy a one-point lead atop the Clausura standings with 25 points from 13 matches.
Santa Fe drop to second, with Medellin a point further back.
Gustavo Costas' Santa Fe started the weekend a point clear of the chasing pack but they were no match for 10-man Nacional.
Luis Paez's goal was good enough for Nacional despite Oscar Murillo's red card with 17 minutes remaining.
Medellin also dropped points as Ayron Del Valle's brace inspired Alianza Petrolera to victory.
German Cano's 67th-minute penalty offered Medellin some hope, though that was quickly extinguished when Cristian Restrepo saw red five minutes later.
Deportivo Cali missed the opportunity to move level on points with Santa Fe following their humiliating 4-0 defeat against lowly Uniautonoma.
Carlos Saa, Jose Amaya, Nelino Tapia and Faber Canaveral were on target for Uniautonoma, who climbed off the foot of the table thanks to their first win in seven outings.
In other results, Millonarios made it back-to-back wins by downing Patriotas Boyaca 3-0.
Aguilas Pereira overcame nine-man Envigado 1-0.
Junior accounted for lowly La Equidad 1-0 courtesy of Yessi Mena's 16th-minute strike.
Nine-man Boyaca Chico lost 2-0 to Atletico Huila, while Fortaleza and Deportes Tolima played out a 1-1 draw.
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