The Dole reign has ended in North Carolina as Democrat Kay Hagan upset incumbent Sen. Elizabeth Dole.
In New Hampshire, Democrat Jeanne Shaheen grabbed another seat for her party in a win against incumbent Republican Sen. John Sununu.
Republicans held on to their contested seat in Kentucky, where Senate Minority Leader Mitch McConnell retained his seat against Democrat Bruce Lunsford.
McConnell's win may help prevent the Democrats from gaining the filibuster-proof 60 total Senate seats that some had predicted, but the new tally already has the Democrats gaining five seats over the 51-49 majority they held going into the election. The balance of power now has Democrats leading Republicans 56-40, with another four races still to be decided tonight.
The high-profile losses of Dole and Sununu were a bitter pill for the GOP to swallow.
Having served in both President Ronald Reagan's and George H.W. Bush's administrations before becoming the first female senator from North Carolina, Dole's legacy seemed almost impossible to overcome when the campaign season began.
But a large turnout of early African-American voters in North Carolina offered an indication that Sen. Barack Obama's relentless campaigning in the state may have paid off for Hagan.
"This is an example of a Democratic senator riding on Obama's coattails," said Jennifer Duffy, the senior editor at The Cook Political Report. "At least 500,000 early voters have been African-American, and Elizabeth Dole isn't getting those votes."
A negative campaign ad released by Dole just days before election that referred to Hagan as "godless" created controversy and may have led to Dole's demise.
In the ad, Dole suggested that Hagan received money from the "Godless Americans" PAC, and an actress with a voice similar to Hagan's was heard saying, "There is no God."
In an ad of her own later that same day, Hagan defended herself and called Dole's add "offensive."
"I believe in God," Hagan says in the ad. "I taught Sunday School."
"My faith guides my life and Sen. Dole knows it," said Hagan, who has since filed a defamation lawsuit against Dole over the ad.
In New Hampshire, polling numbers showed Shaheen leading Sununu throughout the race.
Despite Sununu's well-known name -- his father once helped run the White House, and the Sununu family is as prominent as you get in state Republican quarters -- he was unable to fend off the Democratic challenger.
In the days leading up to the election, presidential historian Julian Zelizer said that "A loss for Sununu would be a lost Northeastern Republican."
McConnell's win was a big one for Republicans.
Symbolically, political experts said a Democratic win in Kentucky would have been "a great defeat" for Republicans, and losing one of the party's most powerful members would strike a significant blow.
Democrats head into this Election Day hoping to widen the majorities they hold in both chambers of Congress when voters go to the polls even holding out a glimmer of hope for a filibuster-proof 60-seat majority in the Senate.
And if they do, it would mean ousting some GOP stalwarts.
With a 51-49 Senate majority before Election Day, if Democrats hold all of their own seats and pick up nine more today -- a tall order indeed -- they would reach a filibuster-proof 60, at least on the occasions that the party votes in unison.