The two greats of the game will play each other after the 23-times major champion confirmed she will participate in the team event with Frances Tiafoe.
Serena Williams is set to begin her 2019 season in Perth after confirmation the American great will play at the Hopman Cup.
Williams, 37, will represent the United States alongside Frances Tiafoe at the team event, which begins on December 29.
The 23-time grand slam champion is set to face Roger Federer on New Year's Day in 2019, when USA meet Switzerland.
"I always enjoy playing in Western Australia and in front of the crowd there at Perth Arena," Williams said.
"The Aussie fans are always so warm and supportive and the Hopman Cup has always given me a great start to the season, especially ahead of the Australian Open.
"I haven't played with Frances in mixed doubles before, but have watched him from afar this year.
"He has a very bright future and I'm looking forward to being on court with him, it will be a lot of fun."
Williams' 2018 season may be over, with the veteran having not played since her incredible US Open final loss to Naomi Osaka last month.
German stars Angelique Kerber and Alexander Zverev are also set to play at the Hopman Cup.