Exit polls released by US media shortly after the first polls closed in Indiana and Kentucky at 6pm (23:00 GMT) indicated that Americans favoured Obama over McCain and the economy was the dominant issue when they made their decision at the ballot box.
Fifty-seven per cent of people surveyed by the Fox News channel thought the Democrat was more in touch with people like them than his Republican rival.
CNN television reported 62 per cent of voters had said that the economy was of most concern to them, followed by Iraq with 10 per cent. Three out of four voters told CBS that the US was on the wrong track under George Bush, the outgoing US president.
Voting ends over the next six hours in the other 48 states.
Election 'upset' vow
Obama has retained a lead in most nationwide opinion polls and has the advantage in most of the battleground states, which are expected to decide the election.
But John McCain, his Republican rival, has dismissed the opinion polls and promised an upset.
Obama cast his ballot at a school gymnasium in his home city of Chicago with his wife and daughter by his side, while McCain voted in his home state of Arizona.
"We're going to work hard until the polls close," the Arizona senator told CBS television.
In an unusual move, both McCain and Obama got back on the campaign trail on election day itself, before planning to head to their respective home bases to watch the results come in.
In Indiana, Obama met campaign workers and made several phone calls to undecided voters, warning the race was going to be tight.
"The question is: 'who wants it more?'" he told about 30 union activists gathered in a campaign office.
McCain campaigned in Colorado and New Mexico.
Joe Biden, Obama's running-mate, cast his ballot alongside his 91-year-old mother and wife, Jill, in his hometown of Wilmington, Delaware.
Sarah Palin, the Republican vice-presidential candidate, voted in the small town of Wasilla, Alaska, where she began her political career as mayor.
In Missouri, which has voted for the presidential winner in every election since 1904 with just one exception, officials were seeing a massive voter response.
"We do have an unprecedented turnout," Laura Egerdal, communications director for Missouri's secretary of state, said.
"I think today we are easily going to set a record for the sheer number of voters turning out today."
Al Jazeera's Sarah Brown, reporting from Chicago, said: "There are some incredible scenes with lines of voters queueing around the block at some polling stations.
"At some places people started lining up at 5am and had to wait up to two hours to vote. As expected, Obama's hometown is doing him proud - of more than 30 voters polled informally all but one were for the Democratic candidate."
Jean Jensen, Virginia's secretary of state, said the turnot was "phenomenal", noting that up to 40 per cent of the state's registered voters had cast their ballots by 10am.
In Florida, Al Jazeera's Sebastian Walker said voter turnout was high.
"This is an important state, and people are aware of how tight it will be," he said.
"The elderly here have a close alignment with the Republican party and John McCain and, while he is trailing in numerous polls here, Florida is a vital state," he said.
"It is also a state where voting irregularities have been witnessed, and that is still fresh in the minds of many people here."
Despite the huge numbers of voters only a few problems were reported.
In some New Jersey precincts, voters had to use paper ballots because of problems with electronic voting machines.
In Virginia, lawsuits alleging voter suppression have been filed.
A day earlier, a judge refused to extend polling hours or provide extra voting machines to predominantly African-American suburbs, after the National Association for the Advancement of Coloured People (NAACP) had demanded the changes in a federal lawsuit.
The NAACP had argued that minority areas would experience overwhelming turnout and there were not enough electronic machines to cater for all voters.