A 90th-minute goal from Juan Cabezas handed Cali a dramatic 1-0 win over Junior at the Estadio Olimpico Pascual Guerrero on Sunday.
With the match petering out for a draw, Cabezas headed home powerfully from a corner in the first minute of injury time as Cali claimed their third consecutive win.
That win was enough to see Cali move a point clear at the summit with 14 points from seven rounds despite Tolima overturning a three-goal deficit to salvage a 3-3 draw against nine-man Once Caldas.
Tolima were in deep trouble at half-time on Sunday after they conceded three goals during the opening 45 minutes.
Johan Arango's brace and a goal from Sergio Romero had the visiting side on track for a routine victory at the Estadio Manuel Murillo.
But Luis Murillo's second yellow card sparked Tolima's stunning comeback as Andres Ibarguen, Yimmi Chara and Hector Acuna found the back of the net in the final 17 minutes.
Acuna salvaged a point for the home side in the 90th minute after getting a foot to the ball ahead of goalkeeper Jose Cuadrado, before Once Caldas' Camilo Perez saw red a minute later.
Tolima (+4) dropped to third in the standings on goal difference after Medellin (+5) defeated Aguilas Doradas 3-0.
Boyaca Chico are level on 12 points with Once Caldas but ahead due to their superior goal difference following the club's 1-1 draw at Uniautonoma.
In other results, Edwin Cardona, Luis Paez, Sherman Cardenas and Miller Mosquera were all on target as Atletico Nacional routed basement side La Equidad 4-0.
Envigado lost 2-1 at home to Deportivo Pasto, who netted two first-half goals.
Santa Fe and Patriotas Boyaca were both 1-0 winners.
Omar Perez's 64th-minute strike saw Santa Fe past Millonarios, while a Gonzalo Martinez penalty helped 10-man Patriotas Boyaca edge Fortaleza, who had two men sent off inside the first 27 minutes.
Alianza Petrolera and Atletico Huila drew 0-0.