The results will determine whether Trump's Republicans retain control of Congress or Democrats take over one or both chambers, potentially limiting the president's ability to advance his agenda.
The vote is widely seen as a test of Trump's second term.
Polls and nonpartisan analysts have given Democrats an edge in the race for the House of Representatives, while control of the Senate remains uncertain, the Reuters news agency reported.
The Senate contest is being fought across nearly 10 closely contested statewide races, most in traditionally Republican states, according to Reuters.
History is also against the Republicans: the party of the sitting president has lost seats in Congress in all but two midterm elections since World War II.
Trump's approval rating is hovering near its lowest levels, with voter frustration over the war with Iran and the resulting rise in fuel prices weighing on his standing, Reuters reported.
Nearly two years into his second term, Trump has repeatedly urged supporters to "pretend I'm on the ballot"—a message Democratic leaders have been quick to echo.
Since early October, he has held more than two dozen campaign rallies, most of them in states he comfortably won in 2024, Reuters reported.
Republicans, led by Trump, have portrayed Democratic candidates as radical, un-American and even communist, it said.
But polls indicate that voters disapprove of Trump's sweeping import tariffs, many of which have been struck down by courts, as well as his decision to attack Iran in February, which contributed to higher consumer prices.
Republican candidates have meanwhile struggled to distance themselves from some of the president's unpopular policies, according to Reuters.
Democrats and legal observers have warned that Trump, who has repeatedly claimed that various US elections were "rigged" or "stolen," could challenge Tuesday's results if Republicans lose.
All 435 seats in the House of Representatives are being contested, along with 35 of the Senate's 100 seats.
Democrats need to gain at least three seats in the House and four in the Senate to secure majorities in both chambers.
In the Senate, they must also defend all the seats they currently hold while winning in at least two states that Trump carried by double-digit margins in 2024: Alaska, Iowa, Kansas, Nebraska, Ohio, South Carolina and Texas, Reuters reported.
It said opinion polls showed Democrats either narrowly ahead or within striking distance in all seven states.
The outcome may not be clear immediately after polls close. In closely contested races, projections could take hours, days or even weeks, the BBC reported.
Congress consists of two chambers: the House of Representatives, the lower chamber, and the Senate, the upper chamber.
A party needs 218 seats for a majority in the 435-member House. In the Senate, 51 seats constitute an outright majority.
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Source: Reuters, BBC