The Argentinian, playing in his final event before retiring, outlasted seventh-seeded Chilean Nicolas Jarry 7-6(10), 4-6, 6-3 in the first round of the IEB+ Argentina Open.
Among the day's other winners on the clay were top seed Alex Zverev of Germany, a 6-4, 6-4 winner over Serbia's Dusan Lajovic, and Brazilian Joao Fonseca, who downed number eight seed Tomas Martin Etcheverry of Argentina 6-3, 6-3 to become the third-youngest winner in the tournament's history at 18 years and five months old.
Fourth-seeded Alejandro Tabilo of Chile and sixth-seed Sebastian Baez of Argentina were upset, while fifth-seeded Francisco Cerundolo of Argentina beat his brother Juan Manuel Cerundolo 6-2, 6-3.
Delray Beach Open
Third-seeded Alex Michelsen, a 20-year-old from California, beat fellow American Michael Mmoh when the latter retired in the second set to advance to the quarterfinals of the hardcourt tournament in Florida.
Mmoh won the first set 7-6(8), then retired with Michelsen up 3-0 in the second set.
All but one of the seeded players in action held court, with fifth-seeded Marcos Giron beating fellow American Ethan Quinn in straight sets, 6-3, 6-4, and seventh-seed Miomir Kecmanovic of Serbia advancing past Japan's Yoshihito Nishioka in a walkover.
France's Arthur Rinderknech was the only seeded player to lose as the ninth seed went down in straight sets to Great Britain's Cameron Norrie 7-6(9), 6-2.
Open 13 Provence
Hamad Medjedovic of Serbia knocked off third-seeded Karen Khachanov of Russia in impressive fashion, winning 6-2, 6-3 to move on to the quarterfinals of the indoor hardcourt tournament in Marseille, France.
Second-seeded Frenchman Ugo Humbert avoided an upset, topping Alexander Bublik of Kazakhstan 7-6(7), 6-4. The only other-seeded player on the court Wednesday, seventh seed Lorenzo Sonego of Italy, picked up the win when French opponent Luca van Assche withdrew.
Medjedovic will next face Germany's Daniel Altmaier, a 6-4, 6-3 winner over Otto Virtanen of Finland.