Nearly 20,000 polling stations have opened for 10.4 million eligible voters, who will cast ballots for a president and a 310-member parliament.
The battle for presidency is a race primarily between incumbent Yoweri Museveni and his main challenger, opposition leader Kizza Besigye.
Security has been stepped up around the capital Kampala with fears of violence running high.
About 12,000 army reservists joined active-duty police and military at polling stations.
However, the troop deployment prompted criticism from the opposition that said the heavy military presence would be used to intimidate voters.
The election campaign was punctuated by sporadic violence between its supporters and security forces.
Diplomats and rights groups earlier warned of fresh unrest and the national election board appealed for calm on and after polling day.
Many voters believe the election will see President Yoweri Museveni extend his 20-year hold on power with a new five-year mandate, overcoming a spirited challenge from Mr Besigye, his former personal physician and close political ally who is now his arch-rival.
Mr Besigye's supporters have complained of harrassment and intimidation but insist they have at least enough votes to force a run-off.
"Tension among voters is high and pre-election violence has been on the increase," Human Rights Watch said in a statement.
"The political parties have a duty to prevent further violence."
The US embassy in Kampala urged "caution" and noted: "There remains a potential for unrest as the elections draw near and in the period following the election when votes are being tabulated and results announced."
Election Commission chairman Badru Kiggundu appealed for calm at a news conference and told reporters that authorities "will not hesitate to take action against any form of violence."
Museveni effectively banned political parties when he seized power in 1986, blaming them for spreading secterian hatred and leading Uganda into disaster in the 1970s, under the rule of then dictator Idi Amin.
A referendum last July brought back multi-party politics.