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.
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.
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.
