The first signs will come from key congressional races on the east coast in suburban Virginia, New Jersey, Florida and NY, however this will likely be a long day.
Anxious Republicans have privately expressed confidence in their narrow Senate majority but fear the House is slipping away.
New Mexico's 2nd district is another key race: Susie Lee, a Democrat, is facing Republican Danny Tarkanian for the House seat held by Democrat Jacky Rosen, who is challenging Dean Heller, and Nevada's 4th district, where GOP candidate Cresent Hardy is facing off against Democrat Steven Horsford.
In Indiana's high-profile US Senate contest, Democratic incumbent Joe Donnelly is seeking reelection against businessman and former legislator Mike Braun.
Aides set up televisions in the White House residence for Trump, first lady Melania Trump and their guests to watch election results come in, with the sets tuned to different cable news channels. Republicans are expected to hold 52 Senate seats and to retain their majority.
In Florida, six House seats are in play, and there are close and crucial battles for a Senate seat and the governorship.
After a divisive campaign marked by fierce clashes over race, immigration and other cultural issues, Americans voted on Tuesday to determine the balance of power in the US Congress and shape the future of Donald Trump's presidency. In the last such congressional elections in 2014, there were 27.5 million early votes. She urged voters to "vote against radicalism, bigotry, and corruption" and "for fantastic candidates all over the country - including a historic number of women".
It was the first national election in the United States since the 2016 race in which Russian Federation interfered, according to USA intelligence agencies, with a campaign of hacking and propaganda to sow discord, harm the Democratic presidential candidate and boost Mr Trump's chances.
He bet big on a xenophobic closing message, warning of an immigrant "invasion" that promised to spread violent crime and drugs across the nation.
The Democrats also had history on their side: 2002 was the only midterm election in the past three decades when the party holding the White House gained Senate seats.
In gubernatorial races, Republican Kris Kobach, a Trump ally, was beaten by a Democrat in Kansas. The Justice Department dropped the charges after his trial ended in an hung jury.
The GOP campaign committee distanced itself from eight-term Rep. Steve King of Iowa after racial remarks, and his seat was unexpectedly contested in the final week of the campaign.More news: 'Diablo Immortal' Game Coming To Android, Pre-Register Now
The incumbent Democratic Senator Claire McCaskill is seen as vulnerable and may lose her seat to her Republican challenger Josh Hawley.
But with his party losing its majority in the House, the results represented a bitter setback for Trump after a campaign that became a referendum on his leadership. In the race for a state Supreme Court seat, Democrat Anita Earls appeared poised to win after Chris Anglin and incumbent Barbara Jackson split the Republican vote. All three and Sherrod Brown, a pro-labor senator victorious in OH, are considered potential 2020 Democratic presidential contenders. Potential 2020 Democratic presidential hopefuls who seemed certain to win included Vermont independent Bernie Sanders and New York's Kirsten Gillibrand.
Trump himself noted the energy as he wrapped up a punishing schedule of rallies around the country that were meant to boost Republican candidates - and his own brand heading towards reelection in 2020.
"It's all fragile. Everything I told you, it can be undone and changed by Democrats if they get in", Trump told supporters during a telephone town-hall organized by his campaign before Air Force One took off for Cleveland.
In the broader fight for control in the Trump era, the political and practical stakes on Tuesday were sky high.
Democrats must gain 21 more seats in the 435-member House of Representatives to regain control of the chamber, which is now led by President Donald Trump's Republicans. It will also give Trump's opponents more scope to investigate his behaviour.
Some Democrats have already vowed to force the release of his tax returns.
But their algorithm has also given them an equally strong chance of retaining control of the Senate. Indeed, more than 100 women could be elected in the House for the first time.
AP VoteCast is a nationwide survey of more than 120,000 voters and nonvoters conducted for the AP by NORC at the University of Chicago. Voters scored Trump positively on the economy and for standing up "for what he believes in".
Even passing many bills will be hard for the Senate.
Democrats Joe Manchin in West Virginia and Tammy Baldwin in Wisconsin won their Senate re-election bids, both states Trump won in 2016.
Democrats boasted record diversity on ballots.
USA voters elected two Muslim women, both Democrats, to Congress on Tuesday, marking a historic first in a country where anti-Muslim rhetoric has been on the rise, American networks reported.