Vinci started her US Open Series at the Canadian Open. Seeded seventh, she lost in the third round to world No. 33, Daria Kasatkina, 5–7, 3–6. Representing Italy at the Rio Olympics, Vinci was defeated in the first round by Anna Karolína Schmiedlová, 7–5, 6–4. Seeded sixth at the Western & Southern Open, Vinci was defeated in the third round by ninth seed Carla Suárez Navarro, 6–1, 7–5. Seeded second at the Connecticut Open, Vinci lost in the quarterfinals to qualifier Johanna Larsson 6–7, 1–6. Vinci was seeded seventh at the US Open, where she has finalist points to defend from last year. She reached the quarterfinals for the fourth time in five years, defeating Anna-Lena Friedsam, Christina McHale, Carina Witthöft, and Lesia Tsurenko. Vinci then lost in the quarterfinals to second seed and eventual champion Angelique Kerber, 5–7, 0–6. As a result, Vinci failed to defend her finalist points from last year, so she fell from the top 10.