Wickmayer started her US Open Series at the Citi Open where she was the seventh seed. She reached the final after wins over Madison Brengle, Zhang Shuai, fourth seed Kristina Mladenovic, and sixth seed Yulia Putintseva. In the final, she defeated Lauren Davis in straight sets. This was Wickmayer's fifth career WTA Tour singles title. In doubles, partnering with Monica Niculescu, she and Niculescu both won the 2016 Citi Open doubles title defeating Shuko Aoyama/Risa Ozaki in the final. Ranked 36 at the Rogers Cup, Wickmayer lost in the first round to qualifier Kristina Kučová. Representing Belgium at the Rio Olympics, Wickmayer was defeated in the first round by Barbora Strýcová. In doubles, she teamed with Flipkens. They reached the second round where they lost to fourth seeds Muguruza/Suárez Navarro. Ranked 38 at the US Open, Wickmayer lost in the first round to Julia Görges.