[4] Bryan played for Stanford University in 1997 and 1998, where he helped the Cardinal win back-to-back NCAA team championships.

In 2005, he and Bob made it to the finals of all four Grand Slam tournaments, only the second time such a feat has been achieved in the Open era.

In his brother's absence, Bryan partnered with several other players, namely Sam Querrey at Roland Garros, Jack Sock at Queen's, Wimbledon and the US Open, Ryan Harrison during the Davis Cup, and with James Cerretani, Frances Tiafoe and Édouard Roger-Vasselin at other tour events.

They went on to play for the Newport Beach Breakers in 2004, the Kansas City Explorers from 2005 to 2012, the Texas Wild in 2013, the San Diego Aviators in 2014, the California Dream in 2015, the Washington Kastles from 2016 to 2018, and most recently the Vegas Rollers in 2019.

It was announced that Bryan, along with twin brother Bob, will be joining the Vegas Rollers during the 2020 WTT season set to begin July 12 at The Greenbrier.

[11] Together with his twin brother Bob Bryan, the pair has won the most Davis Cup matches of any team in doubles for the United States.

In 2012, by winning the Olympic gold medal, along with his brother, Bryan completed the career "Golden Slam", as did Bob.