While some victories were easily won, outcomes of other races did not become clear until Wednesday.
In one of the most closely watched battles across the country, South Dakota Senate Minority Leader Tom Daschle lost his seat to former GOP Rep. John Thune by 4,535 votes -- the first time a party leader has been defeated in 52 years, according to the Associated Press.
Daschle told supporters Wednesday morning he was "grateful for the extraordinary opportunity" from voters, the AP reported.
In Florida, after another close race for the Senate, Democrat Betty Castor conceded defeat Wednesday morning to Mel Martinez, who had already claimed a victory.
The two were battling for retiring Democrat Sen. Bob Graham's seat. Castor won 48 percent of the vote to Martinez's 49 percent. Martinez, who left President Bush's Cabinet to run for office, will become the nation's first Cuban-American senator.
In Kentucky, Republican Sen. Jim Bunning defeated Democratic state Sen. Daniel Mongiarado, despite a string of recent bizarre comments from Bunning, saying his opponent resembled one of Saddam Hussein's sons and that terrorists struck the United States on Nov. 11.
In total, 34 Senate races were at stake last night. Democrats had hoped to claim victory in the few races considered close and build on their 48 seats. There is one Democrat-leaning independent.
Instead, Republicans swept the South, winning seats in North and South Carolina, Georgia, Louisiana and Florida.
The Democrats did, however, celebrate two wins Tuesday night.
Barack Obama easily won his Senate race in Illinois, building upon his popularity after delivering the keynote speech at the Democrat National Convention last summer. Obama defeated Republican Alan Keyes in the first Senate race between two African Americans.
The other gain for Democrats was in Colorado where Attorney General Ken Salazar defeated Republican beer executive Pete Coors by a slim margin.
With Democrats losing ground in Congress and state governorships, they might have to get comfortable with their minority status for awhile, said one Democratic political scientist.
"I think this is a realigning election. The Democrats are going to have to get used to permanent minority status for a generation or two," Tom Schaller, a political scientist at the University of Maryland, Baltimore County, told Reuters.
"The party doesn't know what it stands for any more. The Republicans have built majorities around their ideas, which can be boiled down to a few simple statements. The Democrats fish around for issues where they think there already are majorities," Schaller added.
A Republican political consultant said people in the heartland saw urban Democrats as "smug," according to Reuters.
"If you project a view that people who express strong religious faith are a threat, people who hold that faith are going to feel a sense of resentment," consultant Bill Greener said.
-- Compiled from wire reports and other media sources