In May 2016, Lavezzi was included in Gerardo Martino's final 23-man Argentina squad for the Copa América Centenario. Lavezzi made his first start of the tournament in Argentina's final group match against Bolivia on 14 June, scoring a goal and setting up another in a 3–0 win; he was named "Man of the Match". In the semi-finals of the tournament, a 4–0 win against the hosts United States, Lavezzi opened the scoring in the third minute of play and later set up Gonzalo Higuaín's first goal, although he broke his left elbow after he tumbled over the advertisement boarding while chasing the ball. Due to this injury he was ruled out of the final against Chile where Argentina were defeated 2–4 on penalties following a 0–0 draw after extra time.