Obiang, aged 80, has been in power for more than 43 years — the longest tenure of any living head of state today except for monarchs.
Obiang's re-election seems virtually assured in one of the most authoritarian and enclosed states in the world.
Running against him is Andres Esono Ondo, 61, from the nation's only tolerated opposition party.
The secretary-general of the Convergence for Social Democracy (CPDS) is a candidate for the first time and the sole representative of the muzzled opposition.
Ondo has said he fears "fraud" during voting to elect the president, senators and members of parliament.
The government has leveled its own accusations against the politician, in 2019 accusing him of planning "a coup in Equatorial Guinea with foreign funding."
The third candidate is Buenaventura Monsuy Asumu of the Social Democratic Coalition Party (PCSD), a historic ally of Obiang's ruling party.
The ex-minister is running for the fourth time but has never done well in previous elections. The opposition have called him a "dummy candidate" without a chance.
A few dozen voters had already queued up when the doors swung open at a polling station set up in a school in Malabo's Semu district early in the morning.
"Voting is going well. Everything is normal. All citizens have to vote," fridge repair man Norberto Ondo told AFP.
"I expect this election to bring us prosperity," the 53-year-old added after dropping his ballot in a box at the Nuestra Senora de Bisila school.
As in every election year, security forces have stepped up arrests. State media has justified the crackdown as a bid to counter a "foiled plot" by the opposition to carry out attacks on embassies, petrol stations and the homes of ministers.
In September, after a week-long siege, security forces stormed the home of one of Obiang's main opponents, Gabriel Nse Obiang Obono.
His house had also served as an office for his banned Citizens for Innovation (CI) party.
The assault left five dead — four activists and a policeman, according to the government.
Dozens were injured and more than 150 people were arrested, including Obono.
Leading rights activist Joaquin Elo Ayeto told AFP the incident had "discredited" the electoral process.
"The ruling party needs an 'opposition' to hold sham elections," he said.
Allegations of fraud have plagued past polls.
In 2016, Obiang was re-elected with 93.7 percent of the vote. His PDGE won 99 of the 100 seats in the lower house and all 70 seats in the senate.
In 2009, the president scored more than 95 percent of the vote.