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.
Key Senate States Still Not Yet Projected
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.
The so-called supermajority would allow Democrats to prevent Republicans from slowing or stopping legislation. The last time there was a filibuster-proof Senate was more than 30 years ago in 1977, during President Jimmy Carter's administration.
Even if they don't hit 60, today's voting could earn the Democrats enough seats to at least get close, thanks to the surging popularity at the top of their ticket and the suffering reputation of the GOP. Several experts predict the party has a strong likelihood of picking up seven or eight seats among the 11 most hotly-contested Senate races, putting them on the cusp of achieving a powerful voting majority.
ABCNews.com has focused on several other key Senate races where, if the Democrats succeed, the party will take a strong hold of the Senate.
When Republican Sen. Ted Stevens was found guilty last week on seven felony counts of making false statements in connection with taking money and other favors from supporters, it made the race with Democratic challenger Mark Begich even more of a tossup. But political experts say that even with a political scandal, this race could still go either way.
"One thing that happens when a candidate is in a scandal is that people vote for them because they're seen as an underdog," said Zelizer.
"People could try to defend the state -- between [Republican vice presidential nominee Sarah] Palin and Stevens," said Zelizer.
But Zelizer conceded that because the scandal is at its final stages and "guilty is part of the headline," Republicans may be unable to defend.
But that didn't keep Stevens from trying.
On the eve of Election Day the senator appeared in an infomercial on more than a half-dozen Alaska television stations in an attempt to rally last-minute support.
The two-minute ads showed Stevens telling the people of Alaska: "My Future is in God's hands. Alaska's future is in yours."
We'll likely know who the nation's next president will be by Wednesday morning, but the same is not necessarily true for the next senator from Georgia.
The race in Georgia between incumbent Republican Sen. Saxby Chambliss and Democrat Jim Martin looks increasingly likely to drag on past Election Day.
With third-party Libertarian candidate Allen Buckley pulling votes away from both Chambliss and Martin, it's possible that neither the Democrat nor the Republican will achieve the 50 percent of the vote that is required for victory under Georgia law, stretching the race into a Dec. 2 runoff on and possibly leaving Democrats teetering around the 60 Senate seat mark for nearly a month.
While Obama is not expected to capture Georgia's 15 electoral votes, a recent CNN/Time/ORC poll has him trailing McCain by just 5 percentage points, 52-47. An overwhelming number of African-American voters have turned out to vote early in the state, a result of the Democratic nominees' surging popularity.
"This is a Southern area where Obama's success and excitement could at least close the gap," said Zelizer.
The economy has been another huge issue in Georgia, where Chambliss has been criticized for his support of the $700 billion financial bailout plan that Congress approved last month.
Minnesota is another state where a third-party candidate is complicating the issue. Independent Party candidate Dean Barkley isn't making things easy for Republican incumbent Sen. Norm Coleman and comedian-turned-Democratic challenger Al Franken (yes, that Al Franken).
But Minnesota does not have a 50 percent rule similar to Georgia's, so either Coleman or Franken could win the seat with less that 40 percent of the vote.
Barkley, according to political experts, has been successful in garnering support from voters who are tired of the Coleman and Franken horserace.
"Barkley is sort of the opt out choice for people who are sick of Coleman and Franken," said Duffy. "Watch Barkley's number all night -- I'd expect whoever wins might only win with 38 or 39 percent of the vote."
Duffy adds that while Obama has been doing well in Minnesota -- the Star Tribune/PSRA poll shows him leading McCain 53-42 -- voters in the state have been known to split their tickets.
"I wouldn't be surprised to see Coleman do well even if Obama is doing well," said Duffy.
Zelizer said that while Coleman has remained popular during his tenure in the Senate, he has suffered from "the implosion of the GOP."
The latest poll by the Star Tribune/PSRA on Oct. 31 has Franken leading Coleman 42-38
"Like Dole in North Carolina, Coleman is being dragged down by a party he is often at odds with," Zelizer said.