The victory ensured Guarani ended the penultimate round of the Apertura season seven points clear of Olimpia, who have a game in hand.
Guarani (37 points) sit second in the Division Profesional standings with Olimpia (30) in third ahead of their last two matches of the campaign against Sol de America and Cerro Porteno.
While neither side can catch leaders Libertad, finishing second could be crucial in deciding 2015 Copa Libertadores qualifying, which comes down to aggregate results over the 2014 Apertura and Clausura championships.
The winner of each championship qualifies for the Copa Libertadores, while the third berth is reserved for the next-best team from the cumulative table of the year.
In Asuncion on Tuesday, Guarani hit the front just before the half-hour mark when Octubre's goalkeeper Juanito Alfonso let Sergio Mendoza's long-range strike slip through his fingers.
A fast break in the 71st minute saw Jorge Benitez double Guarani's lead in front of their home fans with the 21-year-old striker having his initial shot saved by Alfonso before tapping home the rebound from a tight angle.
Octubre pulled a goal back with three minutes remaining through Richard Estigarribia but the visitors were unable to find an equaliser.
While Olimpia survived a second-half comeback from 3 de Febrero to win 3-2 on Wednesday, Guarani's victory ensured they cannot be caught in second position.
After Derlis Gonzalez had given Olimpia the lead in the first half, Ever Gonzalez and Cristian Colman struck in the opening 15 minutes after the break to put Febrero 2-1 ahead.
But Diego Centurion's brace in the final eight minutes saw Olimpia triumph at the Estadio Defensores del Chaco.
Libertad (43 points) were held to a scoreless draw by Sol on Thursday but have already wrapped up the Apertura title, while in other results, General Diaz defeated Nacional Asuncion 2-0, Rubio Nu won 1-0 over Deportivo Capiata and Sportivo Luqueno edged past Cerro Porteno 1-0.
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