Former President Tabare Vazquez of the Broad Front, Jose Mujica’s left-leaning party, is ahead in opinion polls.
However, neither Tabare Vazquez nor his main challenger, Luis Lacalle Pou of the right-wing National Party, is expected to win outright without a second round.
Pedro Bordaberry of the Colorado Party is trailing a distant third.
Uruguayans will cast ballots for president, vice-president and members of parliament at the same time. The Broad Front could lose its current majority in Congress.
They will also vote in a controversial referendum on whether to lower the age at which a person can be criminally charged as an adult from 18 to 16.
Jose Mujica remains popular after leading Uruguay through economy growth and wage rises, but he is barred by the constitution from running for a second consecutive term.
His government was behind social reforms such as the legalization of marijuana, abortion and gay marriage.
However, critics say Jose Mujica’s government has failed to deal with problems in education, security and environmental protection.
Polls will open from 08:00 local to 19:30.
If no candidate obtains the 50.1% needed to avoid a second round, Uruguayans will choose between the two leading candidates on November 30.
Tabare Vazquez served as president of Uruguay from 2005 to 2010 while Luis Lacalle Pou is the son of a former president.
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