Forward Eduardo Vargas, defender Marcos Gonzalez and midfielder Arturo Vidal scored for Chile, who leapfrogged Ecuador and now are third in the South American group on 24 points. Argentina and Colombia are joint top with 26.
The top four teams at the end of the qualifiers in October go through to the 2014 Brazil finals. The fifth-placed side go into a playoff against an Asian qualifier in November for one more berth.
Venezuela remain on 16 points and their dream of getting to the World Cup finals for the first time now appears fanciful.
Vargas scored in the 10th minute from Jorge Valdivia's precise cross and rejoiced in defiance of human rights campaigners Amnesty International, who had asked Chile's players not to celebrate their first goal as a gesture to remember the thousands tortured during the dictatorship of Augusto Pinochet.
Pinochet swept to power after a military coup on September 11, 1973.
Centre back Gonzalez doubled the advantage in the 30th minute with a header and Vidal scored six minutes from time with another header after a combination with winger Alexis Sanchez, who crossed from the right.
Venezuela, once known as the South American "Cinderella", were fourth at the 2011 Copa America and made a good start to the qualifiers but they have lost two of their last three, against Uruguay and Chile.