23 time grand slam champion will face Estonian opposition in round two on Thursday.
Serena Williams has won her first match in what will be her final Grand Slam event.
The 40 year old American beat Danka Kovinic in the opening round of the US Open at Flushing Meadows in New York.
Williams came through in straight sets, 6-3, 6-3 and will now face Anetta Kontaveit of Estonia in the next round.
Rafael Nadal is in action later against Rinky Hijikata,
with Carlos Alcaraz to play Sebastian Baez.
Britain's Emma Raducanu will begin the defence of her women's singles title against Alize Cornet.
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