Chileans can decide whether to approve or reject a new constitution and whether it should be drafted by a specially elected citizens' body, made up half of women and half of men, and indigenous representatives, or a mix of citizens and lawmakers.
The winning camp needs a simple majority. Opinion polls suggest a new charter will be approved by a significant margin.
Among the first of a slow trickle of voters was President Sebastian Pinera. His approval rating sank to a historic low during the protests and has remained in the doldrums through the pandemic.
Speaking from the upmarket suburb of Las Condes, close to his home, he urged Chileans to turn out in record numbers regardless of their voting inclination.
"Tonight when we know the results, let us respect the decision of the people and take strong and clear action for democracy and not for anarchy, for peace and not for violence, for unity and not for division," Pinera told reporters.
Jose Antonio Kast, leader of the conservative Republican Party, told reporters as he exercised his vote that if turnout was high, the "reject" camp would win.
"What could have an impact is that people are afraid because of the pandemic. But we are hoping that won't happen," he said.
"The pandemic is bad, but for me what is worse is violence," an elderly voter who gave his name as Jaime told local TV at Santiago's National Stadium, the largest polling station in the country. "I'm open to change but we don't want violence."
Soldiers, ubiquitous on Chile's streets since the declaration of a state of emergency during the protests last year, and again with the outbreak of COVID-19 in March, will oversee the process inside polling stations, while police will guard outside.
Chileans must wear masks by law outside of their homes, and voters have been told to bring their own pens. Voting stations have been sprayed with cleaning solutions containing nanocopper particles, an incorporation of the red metal that is Chile's main export and which is said by scientists to be particularly inhospitable to the coronavirus.
The current constitution was drafted by dictator Augusto Pinochet's close adviser Jaime Guzman in 1980, and has only been tweaked by successive governments to reduce military and executive power.
(Reporting by Aislinn Laing; Editing by Jonathan Oatis and Catherine Evans) ((Aislinn.Laing@thomsonreuters.com; +56 223704250;))