Opposition parties had urged the government to postpone the election because of rising infections, but Suu Kyi, who is the chair of the ruling National League for Democracy (NLD) party, has said the Nov. 8 vote must go ahead.
Wearing a face mask and protective gloves, she voted at a polling station in the administrative capital, where President Win Myint also voted earlier.
The vote is set to serve as a test of Myanmar's first democratic government in half a century and the country's transition away from direct military rule as it grapples with crises on several fronts.
With nearly 50,000 COVID-19 cases and more than 1,000 deaths, Myanmar is facing one of Southeast Asia’s worst outbreaks, and a lockdown has left hundreds of thousands of people without work.
Suu Kyi, who won the Nobel Peace Prize for campaigning for democracy, took the reins in 2016 after an electoral landslide, but has been forced to share power with the generals.
The NLD is expected to win again, though by a smaller margin.
Suu Kyi's international reputation has slumped over Myanmar's treatment of Rohingya Muslims, but she remains popular at home, where her image is undented by accusations of complicity in atrocities against the minority.