Colombia Primera A Wrap: Santa Fe win thriller
Trailing 1-0 heading towards the final 10 minutes, the league leaders pulled out all stops to take all three points - as goals to Jose De La Cuesta and Yulian Anchico sunk the cellar-dwellers.
Rafael Carrascal had earlier given the hosts in Floridablanca an unlikely lead against their powerhouse opponents, but the match ended in disaster for Guillermo Berrio's men.
Atletico Nacional sit second in the table, after beating Envigado 3-2 away from home.
Envigado fought back from an early concession to lead 2-1 via quick-fire first-half penalties from Neider Morantes.
But two goals in two minutes from Santiago Trellez and Juan Valencia gave Atletico all three points, as they made it five wins from six this Apertura season.
Junior slipped four points behind the league leaders in third spot, but preserved their unbeaten campaign with a 2-2 draw away at Medellin.
After conceding twice via Yorleys Mena, Junior hit back twice in two minutes through Luis Ruiz and Juan Dominguez to earn a point.
Once Caldas are level on points with Junior, and are similarly unbeaten with three wins and three draws - most recently held to a stalemate away at Millonarios 1-1.
Patricio Perez struck late to give Once a point, keeping them fourth on goal difference from Boyaca Chico, who lost.
Away at La Equidad, Boyaca Chico fell to a 1-0 defeat, and finished with 10 men when Yeison Gordillo was sent off early in the second half.
La Equidad sit one point behind Boyaca Chico, in sixth place.
Deportivo Pasto have played out four consecutive draws, after striking late to take a point away from Deportes Tolima in a 1-1 result.
Elsewhere, Fortaleza earned a 1-0 road win at Uniautonoma and Patriotas Boyaca beat Itagui 1-0 at home.