Guarani's Fernando Fernandez and Derlis Gonzalez effectively handed the title to Cerro Porteno as they combined to score all five of their team's goals to end Capiata's chances to reaching top spot with two rounds to play.
Cerro Porteno picked up a point with a 1-1 draw against Libertad, which saw the Division Profesional-leaders move nine points clear of Capiata (37 points), while Guarani could still claim second having risen to 33 points.
Capiata had needed three points and for Cerro Porteno not to win to stay in the hunt for the title.
In Asuncion on Sunday, Cerro Porteno led at half-time in front of their home fans through Angel Romero's 32nd-minute strike but Libertad secured a draw thanks to Brian Montenegro's goal just after the hour mark.
That result opened the door for Capiata but they fell behind to the home side in just the seventh minute to a strike from Fernandez.
Dionisio Perez struck back for Capiata three minutes later and the visitors hit the front in the 19th minute through Nestor Gonzalez.
Three goals in the final 20 minutes of the first half - two to Fernandez to complete his hat-trick, plus one to Capiata's Julio Cesar Irrazabal - saw the score reach 3-3 at the break.
But in the second half, Guarani took control with Gonzalez scoring twice, including from the penalty spot in the 71st minute.
Sportivo Luqueno triumphed 4-2 away to Sol de America and Nacional Asuncion defeated Cerro Porteno PF 1-0, while General Diaz and Rubio Nu were both held to 1-1 draws at home by Olimpia and Deportivo Carapegua respectively.
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