Vying for Argentina's first title, del Potro played in the 2016 Davis Cup against Croatia. His first match was a four set victory against Ivo Karlović. Partnering Leonardo Mayer, del Potro lost in doubles against Ivan Dodig and Marin Cilic. 2–1 down in matches, del Potro played in singles against Cilic, coming back from 2 sets down for the first time in his career to win in five sets. Described as one of the best Davis Cup comebacks ever, del Potro levelled the score at 2–2, paving the way for Federico Delbonis to complete the comeback by beating Ivo Karlović in straight sets, thus claiming Argentina's first ever Davis Cup title.