Matias Fernandez opened the scoring after just 14 minutes with a shot from the edge of the box, and nearly doubled the lead ten minutes later when he forced goalkeeper Justo Villar into a great save from his free-kick.
Paraguay nearly drew level on the half-hour mark when Nelson Haedo Valdez' header was cleared off the line by Gary Medel. But shortly after the break Chile consolidated their lead with a headed effort from Humberto Suazo.
Paraguay remain top of the standings with 24 points alongside Brazil, who earlier today destroyed Uruguay 4-0 in Montevideo. Chile move into third place with the win, one behind the leaders and one in front of Argentina, who defeated Colombia 1-0 in Buenos Aires.
Meanwhile, Bolivia played for first time in La Paz since the historic 6-1 victory over Argentina, but they could not live up to such high standards and lost 1-0 to Venezuela thanks to an own goal by defender Ronald Riveros. Riveros put through his own net after a free-kick by midfielder Luis Manuel Seijas in the 32nd minute.
Just over ten minutes earlier Bolivia forward Marcelo Martins missed the chance to put his side ahead from the penalty spot. The evening became worse for Erwin Sanchez' side as both Martins and Leonel Reyes were sent off. Peru take on Ecuador in the final match of the round later today.