But Democrats are hoping to take control of at least the House of Representatives, giving them the opportunity to derail Trump's legislative agenda, and give them power to expand investigations into his personal and professional conduct.
At a polling place in Snellville, Georgia, more than 100 people took turns sitting in children's chairs and on the floor as they waited in line for hours.
It's not clear how big their margin of victory will be in the House.
Republican gains in the Senate are sure to bolster the party's efforts to ram conservative federal judges through confirmation proceedings during a lame duck session that starts next week, as well as next year.
The newly empowered House Democrats will have the ability to investigate Trump's tax returns, possible business conflicts of interest and allegations involving his 2016 campaign's links to Russian Federation.
Democratic victories included the defeat of 11-term Texas Representative Pete Session, the chairman of the Rules Committee, by former professional football player Colin Allred in a Dallas-area district. Dean Heller versus Democrat Jacky Rosen in Nevada; Democrat Kyrsten Sinema versus Republican Martha McSally in Arizona; Democratic Sen.
Trump sought to take credit for retaining the GOP's Senate majority, even as the party's foothold in the more competitive House battlefield appeared to be slipping. A CNN poll released on November 5 found that Democrats led Republicans on a generic ballot by 13 points, 55 percent to 42 percent.
Beto O'Rourke, a charismatic Democrat seeking to dethrone Republican Ted Cruz in Texas, said the state is one of "immigrants, asylum seekers, and refugees".
Trump also touted a booming US economy that continues to pump out jobs and raise average wages But his economic arguments were overshadowed by those appealing to nativist sentiments, such as a promise to end the right of anyone born in the States to citizenship. The Democrats are defending 26 of the 35 Senate seats, which means a good day for the GOP would see them increase their majority the upper chamber.
Sanders, the independent who has always been one of the state's most popular politicians, spent little time campaigning ahead of Tuesday's election.
And in West Virginia - where Trump is wildly popular and campaigned heavily for Republicans - the reelection of Democratic Sen.
Jennifer Wexton, a Democratic state lawmaker, was ahead of two-term Republican incumbent Barbara Comstock by 57% to 43% in their suburban northern Virginia district that Hillary Clinton won in 2016, NBC reported.
Voting begins in crucial midterm polls in US
But the GOP gained ground in the Senate and preserved key governorships, beating back a "blue wave" that never fully materialized. In suburban areas where key House races were decided, voters skewed significantly toward Democrats by a almost 10-point margin.
In Virginia's 7th District, a Republican-leaning area near Richmond, Republican Representative Dave Brat was trailing Democrat Abigail Spanberger, a former Central Intelligence Agency officer. He was defeated by Democrat Debbie Mucarsel-Powell.
You're still up either because Senate returns are really slow, or you are obsessing over Alaska's toss-up gubernatorial race.
Drawing attention like few other midterm contests, the election has pitted competing visions of the country against each other, with race often being front and centre, punctuated by two racially tinged crimes.
Less than a half hour later, the Associated Press projected that Donna Shalala would win the fight for Florida's 27th district, a position vacated by retiring Congresswoman Ileana Ros-Lehtinen.
It was also a sign that the GOP money infrastructure may not have worked its magic: national Republicans stuck with Comstock to the end, spending nearly a half-million dollars in TV ads in the final week.
California Democrats hold 39 of their Party's 193 House seats, or over 20 percent. Democrat and former speaker Nancy Pelosi serves as House minority leader.
All 50 states and Washington DC will go to the polls, and voter turnout is expected to be high. Voters agree. Two-thirds of those casting ballots said their vote was about Trump, according to preliminary exit polls posted by CNN.
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.
Today's elections are the first opportunity for Americans to have a say about Donald Trump's presidency. That could help Democrats because younger voters tend to lean their way.
"Everything we have achieved is at stake tomorrow", Mr Trump told supporters on Monday night in Fort Wayne, Indiana, at one of his three rallies to stoke turnout on the last day before the election. He was active on Twitter throughout much of the day, blasting out endorsements for Republican candidates and weighing in on the balloting.
About 40 million early votes were likely cast, said Michael McDonald, a University of Florida professor who tracks the figures. So, just like in 2016, what many said could not be done could be done once again today.
Despite positive feelings about the economy, overall, voters were pessimistic about the direction of the country.