Biglia was named to Gerardo Martino's 23-man Argentine side that reached the Copa América Centenario Final. He played in the final of the competition against Chile for the full 120-minutes, which ended in a 0–0 draw after extra-time; in the resulting penalty shoot-out, his penalty was saved by Claudio Bravo, and Chile went on to win 4–2 after netting the next kick. Following the end of the tournament, Biglia was among seven players considering retirement after Lionel Messi announced his retirement, but this never happened.