Mattek-Sands has also found great success in mixed doubles; she won the 2012 Australian Open with and the 2015 French Open and a gold medal at the 2016 Rio Olympics. Mattek-Sands then suffered a major knee injury in 2017 that required surgery and a year away from competition to heal, but eventually came back to win the 2018 and 2019 US Open mixed doubles titles, both partnering Jamie Murray. Mattek also played World TeamTennis for the Hartford FoxForce in 2000, the Sacramento Capitals in 2006, and the New York Sportimes in 2008.