On Tuesday, the Republicans lost their majority in the House, Congress's lower chamber, after a Democratic surge during a dramatic midterm campaign season marred by violence and hostile political rhetoric.
They also could force Trump to scale back his legislative ambitions, possibly dooming his promises to fund a border wall with Mexico, pass a second major tax-cut package or carry out his hardline policies on trade.
There was some consolation for Democrats as Senators Joe Manchin and Bob Menendez held on to their seats after tough campaigns in West Virginia and New Jersey respectively.
By 11:30 p.m. Eastern, ABC was reporting Democrats had won 209 seats and Republicans 190 had been elected to the House, making it clear that there would be no "blue wave" as Democrats had been promising for months. In Kansas, Republican Kris Kobach, a Trump ally who was a leader of the president's disbanded voter fraud commission, fell to Democratic state senator Laura Kelly.
Overall, 6 in 10 voters said the country was headed in the wrong direction, but roughly that same number described the national economy as excellent or good. They also attracted a higher proportion of younger voters than at the last midterm elections four years ago and their new lawmakers will make the House younger, more female and more diverse.
In the leadup to the election, Republicans privately expressed confidence in their narrow Senate majority but feared the House could slip away.
Almost 40 per cent of voters cast their ballots to express opposition to the president, according to AP VoteCast, a national survey of the electorate, while about 25 per cent said they voted to express support for Trump.
Speaker Joe Straus, a San Antonio Republican who ousted a fellow Republican with help from House Democrats in 2009, is retiring.
"Tomorrow will be a new day in America", Democratic Leader Nancy Pelosi said at a victory party in Washington.
Democrats were always facing an uphill battle in the Senate this year because they were defending 26 seats, while just nine Republican seats were up for grabs.
The Democrats picked up at least a dozen Republican-held House seats across nearly all regions of the country as returns were still coming in Tuesday but fell short in some closely watched races as they fought to wrest control of the chamber from the GOP. Such a development would divide control of the USA legislature and hinder President Donald Trump's policy agenda for the next two years.
To stem Republican losses, Trump sprinted through mostly white regions of the country, interjecting dark and foreboding warnings about what Democratic power would mean for the nation.
Vermont Sen. Bernie Sanders easily won his third term as he considers another bid for the Democratic presidential nomination.
Trump's Republican coalition is increasingly older, whiter, more male and less likely to have a college degree.
Despite Trump's enthusiasm, it was a mixed night for the GOP.
And in the Senate, triumphant Republicans retained control, ousting Democratic incumbents in IN and North Dakota and ensuring they will remain as guardians of Trump's conservative agenda for two more years.
Democrats also had success in House Districts 23, 24, 28 and 29.
For the State Senate District 22 race, Democrat incumbent Brittany Pettersen comfortably won reelection with 56.96 percent of the votes to Tony Sanchez's 43.4 percent.