Senator Obama and his wife Michelle, with their two daughters looking on, cast their ballots at a polling station in Chicago, while Democratic vice presidential candidate Joe Biden voted in his home state of Delaware.
Senator McCain voted in his home state of Arizona, while his vice presidential running mate Sarah Palin cast her vote in Alaska.
However, although McCain will monitor election results in Arizona, he flew to Colorado where he hoped to be able to overcome a strong Obama showing in a traditionally Republican state.
A more than seven percent increase in registrations since the last presidential election points to a potential record number of Americans participating.
Officials in New Jersey distributed paper ballots to some voters because of problems with electronic voting machines. Other areas encountered minor problems, but officials voiced no major concerns.
In Washington, D.C. American University law student Angela Edmond was part of a volunteer team working to ensure that all those qualified to vote were able to do so. "There was only one problem with a man whose wife had applied for an absentee ballot, and she didn't receive it and she was given a hard time inside. She should be able to vote provisionally, but we're not sure, so we are waiting to see when she comes out.
If he wins the election, Senator Obama at 47 would be the first African-American elected president, while Senator McCain 72 would be the oldest candidate elected president, with Sarah Palin the first woman to be vice president.
Obama addressed tens of thousands of supporters late Monday in Manassas, Virginia, a state no Democrat has won since 1964, but one in which preference polls showed Obama enjoying a significant lead. "I've just got one question for you Virginia. Are you fired up? Are you ready to go? Fired up? Ready to go? Fired up? Ready to go? Fired up? Ready to go? Virginia, let's go change the world. Thank you and God Bless the United States of America," he said.
Senator McCain told television interviewers early Tuesday he believes a tightening of key races gives him a route to victory.
A McCain upset would require a combination of wins across the country, including eight states won by President Bush in previous elections. However, Obama is running strongly in those states.
All 435 seats in the House of Representatives are up for election, with Democrats poised for significant gains there. Republicans are defending 23 of 35 Senate seats at stake.
Democrats could significantly expand their current 36 seat House advantage, potentially achieving their strongest majority in 18 years, and also expect to widen their current narrow margin of control in the Senate.
Polls closing first in Florida, Virginia, Indiana, North Carolina, and Pennsylvania, will deliver early signs of the national trend, although the election result could, depending on developments, also depend on outcomes in the Western United States.