Martin Lasarte's Universidad Chile routed cellar-dwelling Cobreloa 4-0 in their round 14 fixture away from home on Saturday.
Universidad Chile are two points clear at the Apertura summit, having collected 37 points with three matches remaining.
Patricio Rubio made it four goals in three games after doubling the visitors' advantage two minutes shy of the hour-mark.
Audax Italiano were on the verge of a point, when Diego Valdes cancelled out Felipe Flores' 31st-minute opener with nine minutes remaining.
But Argentine midfielder Emiliano Vecchio had other ideas as he restored Colo Colo's lead five minutes from time at Estadio Monumental David Arellano.
In other results, Jean Pineda's 45th-minute penalty lifted fourth-placed Union La Calera to a 1-0 win at home to Universidad Catolica.
Union La Calera (+6) are level on 22 points with O'Higgins (+5) and Palestino (+1), but ahead on goal difference.
O'Higgins overcame nine-man San Marcos 3-1, courtesy of Gaston Lezcano's late brace.
