Camilo Perez was sent off for the hosts in Manizales in the 64th minute, having earned a caution just one minute earlier, and Santa Fe capitalised.
Omar Perez delivered the winner for Gustavo Costas' men, scoring his first goal since September.
Santa Fe are top of Group A after two matches with their perfect record, while Once Caldas sit point-less - bottom of the four-team phase.
In Group B, Medellin went four points clear top after just two matches courtesy of a come-from-behind 2-1 win at Deportes Tolima.
Yimmi Chara put Tolima ahead in the 44th minute, but a second-half revival from Hernan Torres' men saw them take all three points - Yorleys Mena equalising shortly after the interval, before John Hernandez's 78th-minute winner.
Aguilas Pereira came from behind twice for their second draw in the semi-finals phase, in a 2-2 stalemate at Deportivo Cali.
Juan Cabezas put Cali ahead in the 27th minute, and they held the lead to the break.
Brayan Angulo squared it up for the visitors to Santiago de Cali in the 53rd minute, only for Carlos Rivas to reinstate Cali's lead on the hour mark.
But Fabio Rodriguez provided Aguilas' second equaliser of the contest in the 75th minute, as they moved outright second on two points.
