Rodrigo Lopez's sharp finish just after the hour mark on Saturday was enough for Libertad to claim victory away from home, which saw the Asuncion-based club triumph in the Apertura championship.
Libertad finished the weekend four points ahead of Guarani in the table, with just one round of the Apertura season to play, ensuring they will lift the league trophy for the first time since the Clausura campaign of 2012.
Lopez struck the goal that confirmed Libertad's success in the 61st minute at General Diaz's Estadio General Adrian Jara, after the home side failed to clear a free-kick properly and the ball was sent back into the area, where it was nodded down to the 36-year-old striker, who finished past Jorge Luis Gonzalez.
The goal was Lopez's 18th for the season, which dragged him within one strike of the Division Profesional's leading striker Cristian Ovelar of Sol de America.
General Diaz's hopes of claiming a draw were dashed when Eric Valiente was shown a second yellow card in the 78th minute.
Libertad's win means Guarani cannot catch the leaders, despite their 3-1 win over Sol on Saturday.
Miguel Paniagua, Ivan Gonzalez and Jorge Benitez scored for Guarani, while Ovelar hit a penalty for Sol.
The win took Guarani to 43 points with a game remaining, four behind Libertad, while Olimpia moved into third with 33, ahead of Sol and Nacional Asuncion (both 30).
Olimpia defeated Nacional 2-0 on Sunday.
In other results, Sportivo Luqueno were pegged back twice but eventually triumphed 3-2 against 3 de Febrero, Deportivo Capiata defeated Cerro Porteno 1-0 and 12 de Octubre needed a stoppage-time goal to win 2-1 over Rubio Nu.
Get the best features, fun and footballing frolics straight to your inbox every week.