Gustavo Costas' Santa Fe struck twice late on to edge Deportivo Pasto 2-1 at the Estadio Departamental Libertad.
Luis Arias and Wilson Morelo scored after Jorge Ramirez's opener for Pasto, lifting Santa Fe to a one-point lead at the top.
German Cano inspired second-placed Medellin to victory at Millonarios as Once Caldas, who drew 0-0 at second bottom Uniautonoma, dropped to third.
Santa Fe surprisingly fell behind when Ramirez opened the scoring in the 50th minute.
But Arias levelled in the 70th minute and Morelo scored his seventh goal of the campaign soon after to complete the come-from-behind win.
At Millonarios, Cano was the match-winner as his hat-trick saw Medellin to a 4-1 win.
Javier Calle put Medellin ahead with a seventh-minute header before Fernando Uribe's tame shot snuck in to level proceedings.
From the 41st minute, Cano took over as he took his tally for the season to nine goals.
He tapped in the easiest of goals to restore Medellin's lead, finished neatly in a one-on-one and sealed his hat-trick after poor goalkeeping.
Alianza Petrolera made it back-to-back league wins with a 3-1 victory at home to Deportivo Cali and Fortaleza were 2-0 winners at Envigado.
Elsewhere, La Equidad and Aguilas Pereira drew 0-0, Boyaca Chico beat Junior 2-0 and Atletico Huila upset Atletico Nacional 1-0.
Deportes Tolima drew 1-1 at home to Patriotas Boyaca.
