"With the Democrats favourites to take control of the House and the Republicans the Senate, the next couple of years may be far more hard for Trump", Stephen Innes of OANDA noted in an email on Tuesday morning.
But the Republicans could lose up to 10 state gubernatorial races.
Voters will choose their new politicians in the House of Representatives and Senate today.
In the Miami area, former Clinton administration Cabinet member Donna Shalala won an open seat, while GOP Rep. Carlos Curbelo lost his bid for a third term in another district.
Republican Mike Braun opened an early lead in the crucial Senate showdown in IN with incumbent Democrat Joe Donnelly, but the race was too close to call with just 9 per cent of the votes in.
Voting will close in another 18 states at 8pm.
The first national elections since Mr Trump captured the White House in a 2016 upset have become a referendum on the polarising president, and a test of whether Democrats can turn the energy of the liberal anti-Trump resistance into victories at the ballot box.
With the Democratic Party needing a net gain of 23 to take back the House, its candidates flipped seats in several suburban districts outside Washington, Philadelphia, Miami, Chicago and Denver that were considered prime targets for turnover because they were won by Hillary Clinton in 2016.
Since it seems unlikely that the Democrats will win the majority in the Senate, it also doesn't seem likely that the House will spend most of its time focused on passing legislation next year, because if bills "die" in the Senate before making it to the President's desk, few will want to spend much time on bills that won't become law, or at the very least, force the President to issue a veto.
The president has boasted about the economy and hammered away at illegal immigration in the closing days of the campaign as he seeks to retain a congressional majority and salvage his legislative agenda.
Mr Trump has faced widespread criticism for his divisive language.
At stake was control of at least one house in the United States Congress, and with it Trump's ability to drive ahead with an unconventional style of government that has divided Americans like rarely before.
Democratic U.S. Senate candidate Phil Bredesen has cast his vote in Nashville.
Democrats took control of the House of Representatives on Tuesday night, a victory that will transform a Republican-controlled chamber that supported and protected President Donald Trump into a legislative body ready to challenge and investigate him. The Senate, where only 35 seats are up for grabs, has a map that favors the Republicans. "In short, should the Democrats take the House, we can expect more policy gridlock and the revelation of more political scandals", Brown said.
Rachel Barkley, a 30-year-old from Raleigh, said she waited in line for two hours at the Brier Creek Community Center.
Among the key issues that matter to voters, four in 10 people said healthcare topped their list, while 20 percent of people said the economy and immigration was their primary concern, respectively.
"I have worked at this poll the last three elections and this is the biggest turnout ever", said Ms Bev Heidgerken, 67, a volunteer at a polling place in Davenport, Iowa.
From sea to shining sea, there are many close races and questionable outcomes, leading to an evening of nail-biting and deep breathing all around.
Polls are also closed in parts of in, where Democrat Joe Donnelly, a top target of the President's frenetic final midterm election campaign swing, is fighting an uphill battle for re-election against Republican Mike Braun.
However, Gallup finds that Republicans and "Republican leaners", in contrast, are less anxious about what will happen in the USA if Democrats obtain a majority in either house of Congress.
In the aftermath of a deadly shooting at a Pittsburgh synagogue in late October, a progressive Jewish group asked him not to visit the city until he denounced such views; Trump went to Pittsburgh anyway.
Democratic former vice-president Joe Biden called on Americans to use their votes to reject Mr Trump. The former president tweeted the vote "might be the most important of our lifetimes". "I think he's preying upon people's fears".
Voters also punished moderate Senate Democrats running in Trump-heavy states who opposed the confirmation of Brett Kavanaugh to the Supreme Court.
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.
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