At the start of the 2016 season, Duval replaced an injured Serena Williams at the 2016 Hopman Cup. She represented the United States alongside Jack Sock. Although she lost both of her singles matches, Duval and Sock were able to win two out of their three mixed doubles matches, including a victory over the Czech pair of Karolína Plíšková and Jiří Veselý. A month after the tournament, Duval announced she had knee surgery. She made a brief return for the grass court season in the middle of the year, but ended up sitting out another ten months afterwards to return to full health.