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.
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.