The Democrats have won control of the Senate, the Associated Press has called.
Early results indicate the opposition is on the cusp of taking the House of Representatives as well, having flipped a handful of seats previously held by Republicans.
It is a devastating blow to the Republican Party and Donald Trump, who have lost full control of Congress.
The US president will face hurdles during his next two years in office, where he will no longer have the numbers to advance his legislative agenda without bipartisan support.
A Democrat-controlled House is also likely to bring more aggressive oversight of the Trump administration, with more investigations, subpoenas and congressional hearings.
The Republicans, also known as the Grand Old Party or the GOP, headed into the 2026 midterms with a slim majority in each chamber.
Analysts and prediction markets had tipped the Democrats to win the House and possibly the Senate, though a tougher race was anticipated there.
All 435 seats in the House were up for grabs, while just a third of the Senate's 100 seats were being contested.
The Democrats needed a net gain of three seats to take the House and four more seats to win the Senate.
They were successful in flipping more House seats than needed in New Jersey, Ohio, Pennsylvania and North Carolina, as well as in the Republican stronghold of Kentucky.
One of the first Senate seats to flip to the Democrats was in North Carolina, where Roy Cooper beat the GOP's Michael Watley.
The seat was previously held by the GOP's Thom Tillis, who announced his retirement last year after clashing with Mr Trump.
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The Democrats also gained ground in South Carolina's Senate race, where Annie Andrews beat the GOP's Darline Graham — the sister of Lindsey Graham, who died earlier this year while in office.
That result marked a significant victory over the Republicans and Mr Trump's hand-picked candidate, in a state he carried by nearly 18 per cent just two years ago.
A major upset was also seen in Texas, where Democrat James Talarico defeated Republican Ken Paxton.
Mr Talarico became the first blue candidate to win statewide in Texas since 1994, and the first to be elected to the Senate in 38 years.
A fourth Republican Senate seat then fell to the Democrats in Ohio, where challenger Sherrod Brown clinched a victory over incumbent Jon Husted.
Shortly after, another Senate race was called in the red state of Kansas for Democrat Adam Hamilton.
His victory over first-term senator Roger Marshall marks the Democrats' first Senate win in the state of Kansas since 1932.
Democratic candidate Jon Ossoff's re-election in Georgia was another key Senate seat called early in the election.
At his victory party, Mr Ossoff called the Trump administration a "failed lame duck".
"If at times these last two years, amidst the ceaseless onslaught of brutality and decency, you doubted if our republic would survive, let tonight's results give you courage that the first light of dawn is on the horizon," he said.
Shortly after multiple US media outlets projected the Democrats' victory in the House, Mr Trump posted on his Truth Social platform: "I wasn't on the Ballot and if I was, we would have won IN A LANDSLIDE!"
However, in an interview with the New York Times, the US president said he was "absolutely willing to accept" the results.
"We'll work with the Democrats, and we'll, you know, look forward to working with them. We'll probably work something out," he said.
