His running mate, William Ruto, also faces ICC charges.
Despite the indictment, Kenyatta enjoys massive popularity. But some voters are afraid the international community will isolate the nation if a candidate facing ICC charges is elected.
Dominic Muia, 35, was in line at 5 a.m. to cast his ballot in the town of Nakuru.
"My main issue is the economy," he said. "I'm voting for Uhuru because he is younger and has a better vision to move the country forward."
At 51, Kenyatta would be the youngest Kenyan president ever if he wins. Odinga is 68.
'Things average citizens worry about'
Harrison Mario, 37, said his vote is based on issues and policies, and will go to Odinga.
"Basically, he has been fighting for inequality." he said. "He has been campaigning for the less fortunate -- his manifesto focuses on security, education and food -- things an average citizen worries about."
Both leaders are campaigning on almost the same policies, leaving the more than 14 million registered voters to choose based on criteria including personality, ethnicity and links to political parties.
"I don't know that much about their differences, so I'm voting for candidate of my favorite political party," said Susan Kamau, who lives in Nairobi. "In short, I'm voting on loyalty to my party, not issues."
In addition to the presidential race, the nation will also pick a president, governors, senators and a slew of other local candidates under the new constitution.
Whoever wins, the race brings back memories of a political dynasty.
Kenyatta's father was the nation's founding president, while Odinga's father served as his vice president in the 1960s.
Both started out as allies in the fight against independence from Britain, but they had a falling out that led Jomo Kenyatta, a Kikuyu, to force out Jaramogi Odinga, a Luo, as his vice president.
Their tense history has strained relations for decades between Kikuyus and Luos.