It was all the home side from the start with Eduardo Vargas opening the scoring before Marcos Gonzalez scrambled the second goal before the break.
The Venezuelans fought valiantly in the second-half but could not find that elusive goal to get back in the contest as Chile ended the match through Arturo Vidal's late header.
Chile dominated their opponents from the outset with Barcelona attacker Alexis Sanchez and playmaker Jorge Valdivia linking up regularly.
Valdivia created the first goal in the 11th minute with a superb chipped pass to Vargas in the penalty area, who controlled the ball, swivelled and rolled his shot past Venezuelan goalkeeper Daniel Hernandez.
Mario Rondon had Venezuela's best chance of the half on 19 minutes as he blasted into the stands after finding himself goal-side of his markers.
But Chile doubled their advantage when Hernandez parried Arturo Vidal's bullet header to the feet of Gonzalez and the full-back dispatched the rebound into the net on 30 minutes.
Venezuela thought they had pulled a goal back early in the second-half but Rondon's header was controversially disallowed by the referee with no foul apparent on the replays.
Vargas should have finished the game off in the 60th minute but he somehow managed to head Sanchez's back post cross wide with the goal gaping.
Sanchez's pinpoint delivery eventually created the third goal as his looped cross was headed home by a diving Vidal in the dying stages of the match.
Chile move into third place in the CONMEBOL World Cup qualification standings and are now eight points clear of fifth-placed side Uruguay, who occupy the play-off position but have two games in hand.
