Some 41 million people are eligible to vote for a successor to left-wing President Gustavo Petro, who is constitutionally barred from running for a second term.
Campaigning was increasingly overshadowed by a series of attacks, with civilians, soldiers, and police officers killed or injured.
More than 400,000 soldiers and police officers are being deployed to monitor and secure the elections, according to El Tiempo newspaper.
Colombia is experiencing "one of the worst waves of violence in recent years", said Kristin Wesemann, head of the Colombia office of the Konrad Adenauer Foundation (KAS), a German think tank.
Fourteen candidates are running, but there are three clear frontrunners, recent polling shows.
Left-wing Senator Iván Cepeda from the ruling coalition is running against conservative Senator Paloma Valencia from the circle of former President Álvaro Uribe, while right-wing lawyer Abelardo de la Espriella is also standing.
If none of the candidates secures an absolute majority, which seems likely according to current polling, a run-off is to be held on June 21.
Parliamentary elections held in March already showed the depth of polarisation in Colombia. Although Petro's left-wing coalition became the strongest force in the Senate, no party managed to attain a clear majority.
That means the future president is likely to struggle in coalition negotiations.
Preliminary results are expected after voting closes.
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