Democrats grabbed a Republican-held seat in Illinois as they fought to retake control of the Senate from the GOP.
But Republicans held onto seats in Indiana and Florida, and several other key races were too close to call.
In Illinois, GOP Senator Mark Kirk had long been considered the most endangered Republican incumbent, as he faced a strong challenger in a state that favours Democrats in presidential election years.
His opponent, Democratic Congresswom Tammy Duckworth, is a double-amputee Iraq war veteran with a compelling personal story.
In Indiana, GOP Congressman Todd Young beat former Democratic senator and governor Evan Bayh, who mounted a much-ballyhooed comeback bid, but wilted under scrutiny.
And in Florida, GOP Senator Marco Rubio beat Democratic Congressman Patrick Murphy, giving Rubio a platform from which he could mount another bid for president in 2020.
But with several other races too close to call, control of the Senate depended on outcomes in North Carolina, Missouri, New Hampshire and elsewhere as the night wore on.The outcome was not unexpected since Murphy had been abandoned by his own party in the final weeks of the campaign, but polls had tightened heading into Election Day.
In New York, Senator Chuck Schumer, the Democrats' leader-in-waiting for a new Congress, easily won re-election.
Results elsewhere would tell if Schumer leads a Democratic majority in the Senate next year, or a minority when he replaces retiring Nevada Senator Harry Reid in the leader's role.
"I hope the voters of America will bless us with a Democratic majority in the Senate," Schumer told cheering supporters in Manhattan.
The outcomes came as GOP incumbents around the country faced energised Democratic challengers trying to oust them in costly and caustic battles shadowed every step of the way by the polarising presidential race between Republican Donald Trump and Democrat Hillary Clinton.
In GOP-held North Carolina, Missouri and New Hampshire, it looked like it could go either way as voting progressed. The races were also close in Pennsylvania and Nevada, the one Democratic-held seat that was hotly contested this election.
Republicans hold a 54-46 majority in the Senate, including two independent senators who caucus with the Democrats.
That means Democrats need to pick up just four seats to take the majority if Clinton wins the White House and can send her vice president to cast tie-breaking votes in a 50-50 Senate. Democrats would need to pick up five seats if Trump wins.The GOP retook the majority just two years ago.
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