With Cerro Porteno held to a 4-4 draw at Sol de America on Sunday, Libertad finished the third round of the Apertura season leading the Paraguayan league on goal difference.
Libertad led 2-1 at home at half-time and after Rubio Nu had Nelson Ruiz sent off in the 69th minute, the hosts wrapped up victory in second-half stoppage time with a goal from Jorge Daniel Gonzalez.
Pedro Sarabia's Libertad (seven points, plus four goal difference) moved ahead of Cerro Porteno (seven points, plus three), while Nacional Asuncion sit third after a 3-1 win against Deportivo Capiata.
In Asuncion on Saturday, Libertad hit the front in the eighth minute when Jorge Recalde produced a drag-back and pass to Claudio Vargas, who burst in from the right before slotting his shot under Rubio Nu goalkeeper Jorge De Olivera.
Rubio Nu equalised in the 27th minute when Alfred Mazacotte scored from a corner but the visitors could not keep the score level for the rest of the half with Libertad striker Rodrigo Lopez heading home just before the break.
Ruiz was shown his second yellow card with 21 minutes remaining when he slid in with a high boot and Libertad took advantage of their extra player in the 93rd minute, with Gonzalez playing a one-two with Recalde before expertly chipping De Olivera.
Cerro Porteno were denied the chance to return to first place in the standings on Sunday when Cristian Ovelar converted a 94th-minute penalty for Sol de America.
Sol had led 1-0 and 3-1 against the previous league leaders but looked set to lose when Guillermo Beltran, Daniel Guiza and Julio Dos Santos scored for Cerro Porteno within 16 second-half minutes.
But Ovelar's late penalty ensured the match finished 4-4 and maintained Sol's run of draws this season.
Sol have three draws from as many games to sit eighth in the table, while the result ended Cerro Porteno's perfect start to the campaign.
General Diaz and 3 de Febrero both notched their first wins of the season on the weekend with the former accounting for Guarani 3-1, while the latter won 3-2 over 12 de Octubre.
In the other match in round three, Olimpia drew 1-1 with Sportivo Luqueno.
