Last season's fourth-placed side opened their campaign with a 4-2 victory, and there were even more goals on show at the Estadio Luis Troccoli.
River Plate took the lead on 26 minutes when Cristian Techera was on target, but Cerro were ahead at the interval courtesy of goals to Hugo Silveira and Hector Acuna.
Sebastian Taborda swung the momentum back in River Plate's favour after the break, equalising in the 50th minute before converting a spot-kick eight minutes later to put Guillermo Almada's men back in front.
Michael Santos doubled the visitors' advantage with his first league goal of the campaign, following on from his good form in the Copa Sudamericana which has seen him on target twice already this term.
Acuna's second goal - from the spot - made for an entertaining finish, but Diego Casas scored River Plate's fifth to seal the three points.
River Plate sit in fifth but have a game in hand on most of their rivals, with El Tanque Stanley and Nacional topping the table having won three out of three.
El Tanque Stanley claimed a 2-0 win away at Miramar Misiones with Juan Marcarie and Jonathan Iglesias the goalscorers for the league leaders.
Nacional - second only by one goal in differential - had a comfortable 3-1 home win over Sud America.
Richard Porta netted a brace for Nacional, after Ivan Alonso opened the scoring - with Adrian Argacha earning a late consolation for the visitors.
Danubio are unbeaten in third place on seven points, after a 2-1 comeback win away at Liverpool on Saturday.
Rodrigo Aguirre put Liverpool ahead on nine minutes, but Ignacio Gonzalez and Emiliano Velazquez scored late in the first half to put Danubio in front for good.
Racing are fourth after back-to-back wins, most recently chalking up a 2-0 road win at Fenix.
Juventud de Las Piedras earned their first points of the new season, with a 3-1 home victory over Defensor Sporting.
Sporting were looking the goods when Nicolas Olivera netted a penalty on the half-hour mark to have the visitors ahead at the interval.
But Juventud came home with a flourish, as Jaime Baez, Emiliano Romero and Dario Flores all got on the scoresheet - the club's first goals for the campaign.
Rentistas similarly got their points and goals tally off the mark with a 3-2 victory away at Penarol, with Guillermo Maidana scoring a match-winning brace.
Cerro Largo have kicked off their season with consecutive draws, after being held at home to Wanderers 1-1.
