The top four teams qualify automatically for the 2014 finals in Brazil, while the fifth-placed team will face an Asian side in a two-legged play-off for another spot in the tournament.
Striker Eduardo Vargas put the Chileans ahead with a shot from outside the box four minutes before half-time before midfielder Arturo Vidal, who had hit the post in the opening minute, doubled their lead in the 56th minute.
Striker Roque Santa Cruz pulled one back in the 88th minute for Paraguay, who are bottom of the group and have virtually no chance of qualifying for Brazil.
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