Key victories in Senate races Tuesday mean Democrats will keep control of the Senate, CNN projects.
While poll results were still trickling in for some significant races, the Democratic wins will make it impossible for Republicans to regain control of the chamber.
"No chance we get there," a top GOP source told CNN. "We have (a) real possibility of going backwards."
According to CNN projections, Democratic candidate Elizabeth Warren defeated incumbent Republican Sen. Scott Brown in Massachusetts and Democratic Rep. Joe Donnelly scored a major upset in the Indiana Senate race when he won against tea party candidate Richard Mourdock.
Both projected wins are pickups of key Republican seats and critical to Democratic ambitions to maintain their majority control of the Senate.
Democrats also scored notable victories in Virginia, Ohio and Connecticut.
Former Gov. Angus King's victory in Maine's Senate race was another blow to Republicans. King, an independent who quickly rose to frontrunner status, won the seat vacated by retired moderate Republican Sen. Olympia Snowe.
King hasn't said which party he would caucus with in the Senate, but he is widely assumed to align with Democrats.
Considered a shoo-in for re-election, Snowe shocked her colleagues earlier this year when she suddenly announced that she would leave the Senate, which she described as hopelessly partisan.
Two years ago, Republicans had every reason to believe they could take back the Senate this year, after major midterm election gains. But heading into Tuesday, Democrats appeared well-positioned to retain their slim majority, and with it, the ability to influence much of the Washington agenda during the next two years.
There were 33 Senate seats at play on Tuesday.
Brown defeats Mandel in contentious Ohio Senate race
Going into Tuesday's vote, Republicans were protecting only 10 seats, while Democrats were defending 23, many in narrowly divided swing states. In addition, several veteran Democratic incumbents, mostly moderates, announced they would retire, making it potentially even easier for Republicans to win those seats.
Republicans have encountered their own problems.
In August, the campaign of Rep. Todd Akin nearly collapsed after the Missouri Republican's comments about "legitimate rape" and his suggestion that women could biologically prevent pregnancy if they are raped. Until then, Republicans believed Akin would defeat Democratic Sen. Claire McCaskill, who polls showed was not very popular after just one term.
McCaskill defeated Akin at the polls Tuesday, CNN projects.
Mourdock sparked a similar controversy last month when he defended his opposition to abortion even in the case of rape because, "I think even when life begins in that horrible situation of rape, that it is something God intended to happen."
Operatives from both parties agreed that many Senate races would be determined by which presidential candidate carries the state, particularly in key battleground states like Florida, Virginia, Pennsylvania, Wisconsin, and Nevada.
Key Senate race snapshots
Arizona: Rep. Jeff Flake (R) vs. Richard Carmona (D)
Open seat -- Sen. Jon Kyl (R) is retiring
This race turned more competitive than originally expected. Democratic nominee Dr. Richard Carmona, a Vietnam veteran and a former U.S. surgeon general under President George W. Bush, proved to be a formidable opponent to six-term Rep. Jeff Flake, whose tough August primary for the GOP nomination left him bruised as he began the general election.
Tightening polls caused both campaigns to go negative, with Flake accusing Carmona of having anger issues over an incident in which a former HHS official accused him of banging on her door in the middle of the night and scaring her family (Carmona denied the incident ever occurred). Carmona accused Flake of not supporting veterans as a congressman (Flake said Carmona is cherry-picking votes and not looking at his entire record).
Democrats thought their candidate's strengths and the state's growing Hispanic population will lead to their party's first successful Senate election since 1988. But Republicans pointed to no significant changes in Hispanic voting records, Flake's endorsements from Sens. Kyl and John McCain, and the state's traditional GOP support as reasons for a Flake victory.
Connecticut: Rep. Chris Murphy (D) vs. Linda McMahon (R)