Kanepi returned from long injury break in June (having dropped to 630 in WTA rank), she tried herself in the ITF Circuit, winning two ITF titles in Essen, Germany, and Pärnu, Estonia. She then got into the qualification rounds of the Wimbledon Championships, but lost in the second round to Arina Rodionova. Unable to obtain a wild card or protected ranking for the main draw, the Estonian (then ranked No. 421 in the world) received a protected ranking to play in the qualifying for the US Open. She qualified to her first Grand Slam main draw in two years with victories over Nina Stojanović, Louisa Chirico and Hsieh Su-wei. Kanepi recorded victories in her first three main draw matches, defeating Francesca Schiavone (despite being bageled in the opening set), Yanina Wickmayer and Naomi Osaka, reaching the second week at a major since the 2014 US Open. She then defeated Russia's Daria Kasatkina 6–4, 6–4 to advance to her second US Open quarterfinal, her sixth Grand Slam quarterfinal overall, and her first quarterfinal at a major since Wimbledon 2013, where she was defeated in straight sets by Madison Keys. Nonetheless, she made history by becoming only the second qualifier in US Open history to make the quarterfinals and the first to do so since Barbara Gerken in 1981. Following the US Open, Kanepi's ranking skyrocketed from 418 to 110. She managed to finish the year ranked just outside the top 100 (at no. 107), her best end-of-year ranking since 2014.