"McCain put his lifeblood into this state, fought county by county, city by city. He really focused on here, he knew he had to, no Republican has ever been elected president without winning Ohio," John Nichols, Washington correspondent for The Nation newspaper, told Al Jazeera
In Chicago's Grant Park, where Obama was expected to speak, about 65,000 supporters cheered the projections as they were announced. Up to one million more people were expected to throng the streets around the lakeside park to celebrate if Obama wins.
US television networks also indicated that New Mexico and Iowa, both states won by George Bush, the current president, had fallen into Obama's column.
Jesse Jackson Jr, the Obama campaign co-chair, said: "Barack Obama as the 44th president ... it is mindboggling, mindblowing.
"Our children walk into a very different America tomorrow," he told Al Jazeera.
"For some people it is the end of a two-year campaign and for others it has been a 200-year trek ... The civil rights movement, among others, have made this moment possible."
Earlier, media projections had indicated that Obama would take the 21 electoral votes in Pennsylvania, which had been targeted by the Republicans.
"The road to victory for John McCain was to save all of the states President Bush won in 2004 and then try to snatch away a state like Pennsylvania or New Hampshire in order to offset loses in the west later on," Al Jazeera's Rob Reynolds, reporting from Chicago, said.
NBC and Fox News both also projected an Obama win in New Hampshire.
More than 130 million Americans were expected to have cast their ballots on Tuesday.
Laura Egerdal, the communications director for Missouri's secretary of state, said turnout in the poll was "unprecedented".
"I think today we are easily going to set a record for the sheer number of voters turning out today."
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 that 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.
Obama earlier 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.
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.