Gustavo Gomez's 72nd-minute strike was all that separated the two teams at the Estadio Dr Nicolas Leoz.
The result ensured Libertad's six-point gap at the summit, after nine games without defeat to open the season.
Pedro Sarabia's men were forced to share the spoils last week, ending a five-game winning streak.
But after a scoreless first half, Libertad were back on the winners' list thanks to Gomez's effort 18 minutes from time.
The 20-year-old Paraguayan striker was on hand to head home the match-winner, his third goal of the season, and condemn third-placed Asuncion to just their second loss.
Libertad are six points clear of Guarani, who came from behind to beat lowly 3 de Febrero 2-1 on Sunday.
Cesar Llamas had given the visitors an eighth-minute lead before Juan Aguilar and Jorge Benitez guided Guarani to victory at Estadio Rogelio Lorenzo Livieres.
3 de Febrero are now bottom of the table following 12 de Octubre's shock 2-1 win at Sportivo Luqueno.
Sportivo were leading up until the 75th-minute mark before two penalties from Tomas Guzman in the space of eight minutes handed the visitors their first win of the campaign.
In other results over the weekend, Rubio Nu overturned a two-goal deficit to earn a 3-3 draw at home to Cerro Porteno.
Ricardo Ortiz's 75th-minute goal cancelled out Oscar Gamarra's earlier effort as Deportivo Capiata played out a 1-1 draw with General Diaz.
Meanwhile, nine-man Sol de America defied the odds to earn a 1-1 draw at Olimpia.
