Velez took the lead in the first leg of the all-Argentine tie at Newell's Marcelo Bielsa ground in Rosario with a fine goal from 18-year-old winger Agustin Allione in the 63rd minute.
A quick break out of defence saw Jonathan Copete feeding playmaker Federico Insua, who threaded a pass through for Allione to beat goalkeeper Sebastian Perata with a right-footed shot.
Velez right back Fabian Cubero will miss the second leg in Buenos Aires on May 14 after being sent off six minutes from time for a second booking.
Newell's, who beat Velez 3-1 in Buenos Aires on Friday in the domestic championship, hit the bar twice, had a header cleared off the line by Emiliano Papa and saw a shot from defender Vergini tipped over by goalkeeper Sebastian Sosa.
Three-times champions Nacional of Uruguay are away to Real Garcilaso at 3,400 metres above sea level in the Peruvian Andes in the first leg of their tie on Thursday.
Holders Corinthians travel to face six-times champions Boca Juniors at La Bombonera in Buenos Aires next Wednesday, while favourites Atletico Mineiro visit Sao Paulo in an all-Brazilian clash the following day.
- Sports & Recreation
- Buenos Aires
- Agustin Allione
- Marcelo Bielsa
- Jonathan Copete