Pre-election surveys showed ex-general Otto Perez Molina from the Patriotic Party some 20 points ahead of his nearest rival, but he is unlikely to win the 50 percent-plus-one necessary to avoid a run-off vote in November.
Polls opened throughout the impoverished Central American nation at 7:00 am (1300 GMT) and were due to close at 6:00 pm (2400 GMT).
Some 7.3 million Guatemalans were due to cast ballots for both the president and vice president as well as for lawmakers in Congress and hundreds of mayors and municipal officials across the country.
In a televised message, the head of the Supreme Electoral Tribunal, Maria Eugenia Villagran, urged people to get out and vote.
"The day of our national civic holiday has arrived," she declared.
"We call on all our people, especially women, young people and those from the indigenous community to exercise their will through their vote," she said.
While heavily favoured, Perez is unlikely to win the 50 percent-plus-one necessary to avoid a run-off vote in November.
"Let's support safety for all Guatemalans, and lower the violent crime rate," Perez, 60, told a crowd of some 4,000 that gathered at Asuncion Mita, on the border with El Salvador at his final campaign rally held on Friday.
Guatemala is still struggling to emerge from 36 years of civil strife, which ended 15 years ago. Perez was a senior military officer who rose to head of military intelligence before retiring in 2000.
With a population of 14 million -- half of whom live in poverty -- Guatemala is located on major drug trafficking routes between South America and the United States. Guatemala also has a soaring murder rate of about 18 per day, one of the highest in the world, in part blamed on Mexican drug cartels spreading into the Central American country.
Perez running for the Patriotic Party, urged supporters to elect him in the first round of balloting. "By winning the first round, all Guatemalans would win," Perez said. He claimed that the 19 million dollars that would be spent on the run-off vote "could be spent on health, education, highways."
Perez has had a commanding lead in opinion polls since Sandra Torres -- who divorced President Alvaro Colom in a failed attempt to legally run for office -- was disqualified, leaving the centre-left ruling party without a candidate.
Perez will likely face a run-off vote against Eduardo Baldizon, 41, a wealthy businessman who wants the death penalty to be reinstated to end rampant crime.
Third in the surveys ahead of the election is yet another right-winger, physicist and mathematician Eduardo Suger, with about 15 percent support.
Among the crowded field of 10 candidates is Rigoberta Menchu, the indigenous rights activist and 1992 Nobel Peace Prize winner. Menchu, the only leftist on the ballot, has about two percent support among voters.
"Let's vote for a different alternative, to not return to a past of violence," said Menchu, speaking in the town of San Pedro Yepocapa on Friday.
The main task for whoever wins "will be to battle the poverty that we find ourselves in," said Sandra Leticia Castaneda, a 35-year-old housewife in Asuncion Mita.
"Guatemala needs transparency, justice, an end of corruption, and respect for life because public safety is paramount," added 25-year-old Diego Ardon.