Felipe Flores scored the game's only goal on 45 minutes, thumping home from a rebound off Wanderers goalkeeper Gabriel Castellon.
The win maintained Colo Colo's seven-point advantage from second side Universidad Catolica, who posted a 2-0 win over Antofagasta on Saturday.
Jose Munoz and Alvaro Ramos were both on target for Catolica, who sit comfortably in second - five points clear of O'Higgins.
O'Higgins were held to a 0-0 draw at home to Union La Calera, and the result saw them winless in two matches - with Palestino now hot on their heels in fourth, after they snapped a run of four matches without victory.
Palestino, who had not triumphed in the league since early March, posted a 2-0 win away at Nublense, leaving them one point behind O'Higgins.
Deportes Iquique's run of defeats continued, with their third loss in succession coming in the form of a 1-0 reverse at home to bottom club Rangers.
Rangers moved level on points with second-bottom Santiago Wanderers, while fifth-placed Iquique were joined on 22 points by Union Espanola, who enjoyed a 2-1 home success over Universidad Concepcion.
Concepcion fell below Espanola due to the loss, sitting seventh on 21 points.
Huachipato were the weekend's biggest winners, and climbed above Universidad Chile with a 5-2 thrashing of their mid-table rivals.
Universidad Chile led 2-0 at half-time but it was all the Talcahuano hosts after that - with Lucas Simon scoring a brace, while Carlos Espinosa, Omar Merlo and Mauricio Yedro also hit the back of the net.
Cobreloa's three-match winning streak was ended at the hands of Everton, who posted a 2-0 win at home.
Cobresal climbed to 12th in the table, after dispatching of strugglers Audax Italiano 3-1 on the road.
Audax Italiano remain level with Santiago and Rangers on 15 points at the foot of the table.
