Thursday's 1-1 draw away to Paraguayan side Cerro Porteno was enough for River to reach the semi-finals 3-1 on aggregate.
River – seeking back-to-back titles – carried a 2-0 lead into the second leg thanks to goals from Ignacio Fernandez and Rafael Borre in Buenos Aires.
🔥 And then there were 4️⃣. The #Libertadores semifinals are set!— CONMEBOL Libertadores (@TheLibertadores) August 30, 2019
🏆 It's @RiverPlate against @BocaJrsOficial & @Gremio_en against @Flamengo, with spots in @Santiago2019 on the line!
🤔 Who will be contesting the final on November 23rd? pic.twitter.com/uDXpstEZ6U
Cerro Porteno sparked hope of a comeback in the eighth minute when former Borussia Dortmund forward Nelson Valdez put the home side ahead on the night.
Valdez – a 77-time Paraguay international – glanced a header past River goalkeeper Franco Armani.
But Cerro Porteno's hopes were dashed when River midfielder Nicolas De La Cruz scored seven minutes into the second half with a ferocious volley.
River will now go head-to-head with Boca in a blockbuster all-Argentinian Libertadores semi-final.
Boca secured their passage to the penultimate stage on Wednesday night following a 0-0 draw at home to Antonio Valencia's LDU Quito midweek to seal a 3-1 aggregate victory over the Ecuadorian side.
The second leg had to be rearranged and moved to Real Madrid's Santiago Bernabeu in December after the match was twice suspended in November due to an attack on Boca's team bus by supporters.