Defender and substitute German Pezzella scored the game's only goal in the 73rd minute at the Estadio Provincial Juan Gilberto Funes.
The header was all the Torneo Final champions needed in what was an otherwise dull encounter in San Luis, with the win putting them into the 2014 Copa Sudamericana.
San Lorenzo, the Torneo Inicial winners, looked the more dangerous side early on, particularly on the counter-attack.
But the half-chances went begging for Edgardo Bauza's men, who entered the clash on a three-match winless run in all competitions.
There was more life in the contest after the break, but San Lorenzo were fortunate not to be reduced to 10 men.
Defender Fabricio Fontanini's reckless challenge from behind saw him shown a yellow card, yet the biggest punishment was to follow.
Manuel Lanzini curled in an inviting free-kick and Pezzella flicked a header into the far corner to give River the lead and their victory.
