Ismael Benegas' dramatic late winner saw Libertad battle past Olimpia 1-0 at the Estadio Manuel Ferreira on Wednesday.
Pedro Sarabia's men are four points clear at the top, but second-placed Cerro Porteno have a game in hand.
Libertad have just four games left to play, putting them in a good position to secure the title.
They left it until the 92nd minute to secure their latest victory, with Benegas heading in a set-piece to give Libertad the three points.
Cerro Porteno stayed four points adrift, hammering 3 de Febrero 5-0.
Jonathan Fabbro scored a second-half brace for the victors, who ended a run of six matches without a win in all competitions.
At the other end of the table, 12 de Octubre have been relegated after suffering a 4-2 loss at home to Sol de America.
Claudio Correa netted a double for ninth-placed Sol.
Elsewhere, Sportivo Luqueno drew 1-1 against Nacional Asuncion and struggling Rubio Nu played out a 1-1 result at home to General Diaz.
On Thursday, Guarani thrashed Deportivo Capiata 4-1.
