With both chambers of Congress at stake, the results will determine how successfully the next president - Republican Donald Trump or Democrat Kamala Harris - will be able to govern over the next two years before all House seats will again be up for grabs.
Republican Governor Jim Justice was projected to win an open Senate seat in West Virginia shortly after polls closed, which would put the party at 50-50 parity with Democrats in the 100-seat chamber.
The seat was previously held by Joe Manchin, a Democrat-turned-independent.
Republicans on Tuesday picked up one House seat in North Carolina, where Addison McDowell added to their razor-thin majority in that chamber.
West Virginia Governor Jim Justice looks set to bring Republicans closer to controlling the Senate. (AP PHOTO)
Voters made history in Delaware, where they elected Democrat Sarah McBride as the first openly transgender member of Congress.
The balance of power could change over the course of the night as other results come in.
Non-partisan analysts say Republicans stand a good chance of taking back the Senate, where Democrats hold a 51-49 majority.
But Republicans could also lose their grip on the House, where Democrats only need to pick up four seats to take back control of the 435-seat chamber.
As in the presidential election, the outcome will likely be determined by a small slice of voters.
The battle for the Senate hinges on seven contests, while fewer than 40 House races are seen as truly competitive.
Congress will have its first openly transgender member after Sarah McBride was elected to the House. (AP PHOTO)
Democrats are playing defence as they try to retain their hold the Senate, whose members serve six-year terms.
Republicans need to gain only two seats to win control of the chamber, and Justice's victory in West Virginia got them halfway there.
Republicans could secure their majority with a victory in Ohio, where challenger Bernie Moreno held a 51 per cent to 47 per cent lead over incumbent Democrat Sherrod Brown, with 58 per cent of the vote counted.
Republicans also have spent heavily to win Montana, where Democrat Jon Tester faces a tough re-election battle.
Republicans stand a chance to widen their Senate majority further if they win races in several competitive midwestern states.
That would allow them to block many of Harris' initiatives and personnel appointments if she were to win the White House, or help Trump deliver on his promised tax cuts if he wins.
Democrats could easily pick up enough seats to win control of the House, analysts say. (AP PHOTO)
But they are unlikely to end up with the 60-vote majority needed to advance most legislation in the chamber.
In the House, Republicans hold a narrow 220-212 majority.
Analysts say Democrats could easily pick up enough seats to win control of the chamber, though there are no signs of a "wave" election, akin to 2018 or 2010, that would result in a decisive shift in power.
With at least 200 seats safe for each party, the winning side will likely end up with a narrow majority that could make governing difficult.
That has been evident in the past two years as Republican infighting has led to failed votes and leadership turmoil and undercut the party's efforts to cut spending and tighten immigration.
Tight races in the heavily Democratic states of New York and California could determine House control, though the final outcome might not be known for several days as California typically takes several days to count its ballots.