Hosts Nacional dominated the first half and deservedly took a one-goal lead into the break thanks to Orlando Berrio's 34th-minute strike at the Estadio Atanasio Girardot in Colombia.
But Leonardo Pisculichi equalised after 66 minutes to give Argentine Primera Division giants River a priceless away goal heading into next week's return leg in Buenos Aires, where they eliminated bitter-rivals Boca Juniors last month.
Colombian champions Nacional - winners of the Primera A on 14 occasions - claimed the scalp of Sao Paulo to book a spot in the final of South America's second-tier club competition.
Nacional edged Sao Paulo 1-0 in their semi-final first-leg visit to Medellin in November and they looked set to at least repeat that feat when Berrio opened the scoring 11 minutes before half-time.
After being played through by midfielder Edwin Cardona, Berrio fired the ball across River goalkeeper Marcelo Barovero from a tight angle.
It was Berrio's first goal for Nacional since August.
Nacional continued to dictate proceedings before and after the interval, however, they were breached by River, who were rewarded for their hard work.
Just minutes after the home side had struck the bar, Pisculichi received the ball outside the penalty area for River and smashed a half-volley into the back of the net, after Franco Armani failed to deal with it.
River will host Nacional at the Estadio Monumental Antonio Vespucio Liberti on November 10.
‘He instantly popped into our ratings as one of the best U21 midfielders in Europe. The impressive thing is Slot has made him into more of a no.6' Inside Ryan Gravenberch's transformation at Liverpool
‘I don’t think Liverpool would look at Ollie Watkins, a striker isn’t a pressing issue for them – it’s Arsenal who need one’ Former Reds star explains why his old club don’t need an out-and-out forward this summer
