In Pennsylvania, two-term Sen. Rick Santorum, R-Pa., failed to garner more than 45 percent support in most public opinion polls and lost to state Treasurer Bob Casey Jr.
Santorum, once seen as a conservative wunderkind when he was elected to the U.S. Senate at 36, trailed Casey in the polls since the beginning of the campaign.
Despite his efforts to focus on immigration and taxes, Santorum was unable to spark the widespread conservative support that carried him to victory in 1994 and again in 2000.
Another Republican seat fell into Democratic hands in Ohio, where GOP Sen. Mike DeWine went down to defeat.
Trailing in the polls for most of the campaign, reports indicated that national Republican officials had begun scaling back their financial support for DeWine last month. The GOP has denied this, but Rep. Sherrod Brown, a Democrat from northern Ohio, was able to dispatch DeWine with relative ease.
A third Republican, moderate Lincoln Chafee, also fell to the Democratic tide in the northeast, losing to former state Attorney General Sheldon Whitehouse.
Chafee first had to fight back a challenge in his own party by conservative Stephen Laffey, the mayor of Cranston. Chafee gained only a narrow edge in the primary contest and even then needed the support of many national Republicans to do so. Whitehouse used that high-profile support and the widespread disdain for President Bush and the war in Iraq to open up a healthy lead against Chafee.
In Missouri, former state auditor and 2004 gubernatorial candidate Claire McCaskill scored a close and hard-fought victory over freshman Sen. Jim Talent.
Talent took fire for his opposition to stem cell research, a ballot proposition that seemed to bolster support for McCaskill.
Talent had hoped the independent themes he touted while campaigning would resonate with voters who narrowly sent him to the Senate four years ago.
"[M]y view is that people are concerned that the system in Washington is not responding to them, that neither party's establishment is, and they want somebody who will stand up for them and their values and make the system work for them," Talent told the NewsHour last month.
After hours of doubt, a fifth Republican, Conrad Burns in Montana, went down to defeat. Montana Senate President and rancher Jon Tester scored a razor-thin victory over an embattled Republican incumbent Wednesday
With 99 percent of precincts reporting early Wednesday, Tester had 190,486 votes, or 48.9 percent, and Burns had 188,900 votes, or 48.5 percent.
Virginia puts Democrats over the top
Once considered a shoo-in for re-election, Sen. George Allen, R-Va., narrowly lost a brutal campaign against former Navy Secretary Jim Webb. The victory gave the Democrats the last seat they needed to gain a majority in the 110th Senate, a development few analysts predicted before the election.
With 99.8 percent of the votes tallied by 9 a.m. today, Webb held a lead of about 6,860 votes outy of the more than 2.3 million cast -- a difference of three-tenths of a percent.
The narrowness of his lead did not prevent Webb from claiming victory before a hotel of supporters at 1 a.m. Wednesday morning.
"I'd also like to say the votes are in, and we won. This is a great moment for all of us," Webb told the cheering crowd.
At the White House, President Bush admitted the election had been a loss for his GOP.
"It was a thumping," Mr. Bush conceded at the White House. "It's clear the Democrat Party had a good night."
Incumbents rack up victories
In Connecticut, the saga of Sen. Joseph Lieberman continued into a fourth term Tuesday. Lieberman, the Democratic candidate for vice president in 2000, was denied his party's nomination in August when anti-war candidate and millionaire businessman Ned Lamont rode a wave of voter discontent past the three-term incumbent.
Lieberman then filed as an "independent Democrat" on the ballot. The two continued their primary battle throughout the general election, with Republican candidate attorney Allan Schlesinger watching from the sidelines.
Despite national Democratic backing of Lamont, Lieberman rolled to victory on Election Day, pledging to continue to support the Democratic Party even after the leadership abandoned him.
In Maryland, Lt. Gov. Michael Steele, a black Republican, waged a steady and effective campaign in one of the most Democratic states in the nation, but came up short against Rep. Ben Cardin, D-Md., in the fight to replace retiring Democrat Paul Sarbanes.
According to New York Times columnist David Brooks, Steele has been very successful at "carving out an anti-party independent role ... a strong theme to look for in years ahead."
Steele was successful in closing the gap to within a few points. In the end, Cardin rode a tide of Democratic support to a seat in the Senate.
In New Jersey, Democrat Sen. Bob Menendez, appointed to his New Jersey seat just 10 months ago, scored a narrow re-election victory. In a year where President Bush's performance and the war in Iraq dominated campaigns, a homegrown scandal threatened to derail Democratic hopes. The state's party has been hit recently with corruption scandals and Menendez's Republican rival, Tom Kean Jr., made ethics the centerpiece of his campaign, accusing the Democrat of having ties to corruption in Hudson County.
In Vermont, socialist Bernie Sanders, the seven-term congressman, cruised to victory to replace retiring Sen. Jim Jeffords. The election keeps an independent candidate who votes largely with the Democrats in the Vermont Senate seat.
In Indiana, Republican Richard Lugar was declared the winner just after polls closed. The five-term incumbent ran unopposed in a state where several Republican congressmen were battling for their political lives.
As in years past, many incumbent senators cruised to re-election and other seats that were not seriously challenged remained in that party's hands. In West Virginia, Democratic Sen. Robert Byrd, the Senate's longest-serving member, was elected to a sixth term. Democratic Sens. Ben Nelson in Florida and Edward Kennedy in Massachusetts also scored easy victories and Sen. Olympia Snowe appeared to be one of the few New England Republicans to emerge from the 2006 elections with ease.
Additionally, Sen. Trent Lott, R-Miss., scored a clear victory and Thomas Carper, the former Democratic governor of Delaware, also easily won his second term in the U.S. Senate.
Democrats also maintained the seats they held along the West Coast. In California, Washington and Hawaii, Democratic incumbents Diane Feinstein, Maria Cantwell and Daniel Akaka all won re-election.
GOP holds several key races
In Tennessee, Democratic hopes for a Southern victory had dimmed in recent weeks and, indeed, on election night Rep. Harold Ford Jr. came up short in his campaign against former Chattanooga Mayor and Republican Bob Corker.
In Arizona, GOP Sen. Jon Kyl, for much of the campaign seen as a shoo-in, had a late scare by little-known Democratic rival, John Pederson.
Pederson ran a tough campaign, but Kyl's focus on immigration helped keep him in the Senate for another term.