Having taken a 1-0 lead to their away leg in Paraguay, Universidad claimed a 3-2 away win in the second leg - although the damage was virtually done by Ramon Fernandez's goal on 53 minutes.
It was a day for players named Fernandez at the Estadio Defensores del Chaco, as Fernando Fernandez opened the scoring for Guarani, levelling the tie at 1-1.
The Guarani man nodded home a scrappy short cross from Jorge Mendoza, to leave the tie evenly poised with 45 minutes to play.
But his namesake soon handed Universidad a monumental boost, as Ramon Fernandez's goal carried the weight of being scored away from home, and meant the hosts required two goals without reply if they were to advance.
Fernandez thumped a long-range strike with his right boot into the left side of Guarani's net to make it 1-1 on the night, and 2-1 overall.
Jorge Benitez gave Guarani hope of a comeback, as his 65th-minute strike renewed parity at 2-2, save for the away goals rule still benefitting Universidad.
And the Chilean club sealed progression via late goals to Isaac Diaz and Patricio Rubio, as Universidad earned a berth in Group Five alongside Brazil's Cruzeiro, Uruguay's Defensor Sporting and Peru's Real Garcilaso.
Lanus saw off Caracas 3-0, after winning the second leg 1-0 at home in Buenos Aires.
The Argentine club earned the victory via Victor Ayala's 71st-minute strike, with Caracas - of Venezuela - unable to score in the 180-minute play-off.
Lanus joins Group Three, and faces clashes with Paraguay's Cerro Porteno, Chilean side O'Higgins and Colombian outfit Deportivo Cali.
