Polls have closed in most of the US, with early results showing Donald Trump having a slight edge over Kamala Harris.
The final outcome will rest with the results in swing states such as Michigan, Pennsylvania and Nevada.
Prime Minister Anthony Albanese said the federal government would work closely with the future US administration.
"The election of a new president of the United States is always a moment of profound consequence for the world, for our region and for Australia," Mr Albanese told parliament on Wednesday.
"Our government will seek and build a strong partnership with whoever the American people choose as their next president.
"The alliance between Australia and the United States has always been bigger than individuals, that have stood tall through generations of governments from both sides of the aisle."
Opposition Leader Peter Dutton said the alliance with the US would endure.
"It will strengthen, and we will make sure that we work very closely with the incoming administration," he told parliament.
"We want to see the best outcome for the United States because when our close ally is strong and at its best, the world is in its best possible position."
The spectacle of US politics and the nation's cultural power has captured the world's attention. (Lukas Coch/AAP PHOTOS)
Former Australian ambassador to the US Joe Hockey said while voters had been fatigued by the drawn-out campaign, the election result would be driven by a few key issues.
"The economy is always going to be the number one issue and it is right around the world - that's pretty consistent," he told Sky News.
"If Donald Trump had run a better campaign, he would have more effectively prosecuted the case that Kamala Harris is part of the incumbent government.
"There's no doubt the Democrats have prosecuted very effectively the case that the Republicans are in a mess on abortion. It is a hugely divisive issue."
US ambassador to Australia Caroline Kennedy says the presidential race is one of the most significant in American political history.
"This is a historic election, no doubt about it," she told Seven.
"In terms of our foreign policy, and especially in terms of Australia which is our most trusted and capable ally, I don't think it will change the fundamentals ... no matter who wins, Australia will be the winner."
Treasury secretary Steven Kennedy confirmed his department had modelled the impact of the outcome of the US election on the Australian economy.
Mr Trump's proposed tariffs on US trading partners would have the most obvious impact of the policies announced by the two candidates, he told a Senate hearing.
US citizens in Australia are holding election parties in the major capitals. (Dan Himbrechts/AAP PHOTOS)
"A significant increase in tariffs would have implications for both the US economy and, for example, if the tariffs were placed on Chinese goods, for China, and there would be flow-on consequences for Australia," he said.
"In broad terms, the imposition of trade restrictions, such as tariffs typically lead to lower growth and higher inflation."
The prime minister also paid tribute to outgoing US President Joe Biden.
"Though President Biden has several months left in his presidency, I do want to acknowledge his lifetime of service to the American people. His has been an extraordinary contribution," Mr Albanese said.