At 12.30pm AEDT, polls had closed in 11 states and results were beginning to roll in.
Democrat and former North Carolina Governor Roy Cooper defeated Republican Michael Whatley in North Carolina, where incumbent Republican Thom Tillis is retiring.
It gives the Democrats a key victory as they try to flip four seats in the Senate and three seats in the House to wrest control of the chambers from Republicans.
In Georgia, Democrat Senator Jon Ossoff won re-election, defeating Republican Mike Collins and denying the reds a seat they had once seen as a top pickup opportunity.
In New Hampshire, where Democrat Jeanne Shaheen is retiring, Democratic US Representative Chris Pappas defeated former US Senator John Sununu.
The elections could strip President Donald Trump's Republicans of control of Congress, with Democrats favoured to capture the House.
It remains up in the air whether Democrats can seize both chambers.
History is against Trump's Republicans with the president's party losing ground in Congress in all but two midterms since World War Two.
Trump's approval rating is hovering near his career lows, with voters frustrated by war with Iran, higher fuel prices and wider affordability concerns.
There is little doubt the election is all about Trump, nearly halfway through his second four-year term. Trump himself has told his supporters to "pretend I'm on the ballot," a message Democratic leaders have happily echoed.
In televised remarks that appeared aimed at swaying voters unhappy with US support for Israel, Trump said that he intended to stop $US3.8 billion ($A5.4 billion) in promised annual funding to Israel but it was unclear how he would do so, given a 2020 law mandating the funding levels.
The close US-Israel alliance has been a particular focus in Michigan, where progressive Democrat Abdul El-Sayed, who would become the first Muslim US senator if elected, has faced millions of dollars in opposition spending from Israel-linked groups.
Republicans have portrayed El-Sayed and other Democratic candidates as radical, un-American and even communist, labels that Democrats dismiss as Trump hyperbole.
Polls show voters are most concerned about affordability and disapprove of Trump's tariffs on imports and his decision to attack Iran which spiked inflation.
Legal observers and Democrats have warned that Trump, who has long falsely claimed that US elections are rigged, may attempt to challenge Tuesday's results if Republicans lose.
The US Justice Department said it had deployed 1,000 election monitors and observers to all 50 states in what it called the largest Election Day monitoring effort in history.
Democrats criticised the plan as potential voter intimidation.
All 435 seats in the US House of Representatives are up for election, along with 35 of the Senate's 100 seats, though most contests are not considered competitive. Democrats must flip at least three House seats and four Senate seats to win a majority in each chamber.
Democrats have little margin for error in the Senate. The party must defend all of its current seats while winning at least two states that voted for Trump by a double-digit margin two years ago: Alaska, Iowa, Kansas, Nebraska, Ohio, South Carolina and Texas.
There are 47 US House races widely seen as competitive, according to a Reuters analysis of the leading election forecasters. If the other contests all proceed as predicted, Democrats would need to win only 13 of those races to secure a majority.
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