In Missouri, Democrat Claire McCaskill defeated Republican incumbent Sen. Jim Talent early Wednesday morning, in one of the last undecided Senate races.
Control of the Senate now hinges on Montana and Virginia, which remain too close to call.
Democrats must win both of those races to take over the Senate. If they were to win one seat, it would produce a 50-50 Senate – including two independents expected to vote with the Democrats – with Vice President Dick Cheney wielding tie-breaking authority.
In Virginia, the race between Republican incumbent Sen. George Allen and Democrat James Webb appeared likely to be decided by absentee ballots. With almost every precinct reporting, Webb had a lead of about 7,800 votes.
In Montana, Democrat Jim Tester held a 2,000 vote lead over GOP Sen. Conrad Burns with 90 percent of precincts reporting results.
On the House side, Democrats will win at least 26 Republican-held seats, more than the 15 they needed to take over the House for the first time since 1994.
"We are on the brink of a great Democratic victory," said Nancy Pelosi, D-Calif., who's in line to become the country's first female House speaker.
"It's been kind of rough out there," conceded the top House Republican, Speaker Dennis Hastert, who won an 11th two-year term.
So far, Democrats have not lost a single seat in the House or Senate.
Democrats earlier picked up four of the six Senate seats — Ohio, Pennsylvania, Rhode Island and Missouri — they needed to form a majority.
One big Senate contest went to the Republicans, with Bob Corker the estimated winner over Democratic Rep. Harold Ford, Jr., in Tennessee.
Exit polls showed voters perceived theas a nationalized election, with most voters saying national issues outweighed local ones.
Most said President Bush was a factor in their vote, and more cast ballots to oppose him than to support him. Most voters said they were angry or dissatisfied with the administration.
A majority of voters, 56 percent, said they disapproved of the war in Iraq. As expected, voters who supported the war backed Republicans and those who disapproved of it backed Democrats.
"It is all about the president and the war in Iraq," said CBS News chief Washington correspondent Bob Schieffer.
Most voters said they had made up their minds about their votes last month or before.
"We're seeing a huge turn in independent voters to the Democrats," said CBS News political consultant Stu Rothenberg. "National exit polls show a significant advantage for Democratic candidates."
In Pennsylvania, Sen. Rick Santorum, the No. 3 Republican in the Senate and one of its most conservative members, was a projected loser after two terms to Bob Casey Jr., the state treasurer. In Ohio, Sen. Mike DeWine lost to Democrat Rep. Sherrod Brown, a congressman strongly opposed to free-trade agreements, CBS News estimates.
In Rhode Island, Democrat Sheldon Whitehouse was the projected winner over Republican Sen. Lincoln Chafee.
Democrats were projected to hold two Senate seats they were in danger of losing, with Sen. Robert Menendez winning reelection in New Jersey and Rep. Ben Cardin winning a vacant Senate seat in Maryland.
In the comeback story of the night, Sen. Joe Lieberman of Connecticut, who ran as a third-party candidate after losing to businessman Ned Lamont in the Democratic primary, will defeat Lamont in the general election, CBS News estimates.
In a close contest in Arizona, CBS News estimates Republican Sen. Jon Kyl will hold his seat.
On the House side, Republican incumbents went down in nearly every region of the country. Three GOP congressmen were projected losers in Indiana, two in New Hampshire and one in North Carolina. Also, a Democrat won an open seat in Arizona.
Ethics woes were clearly taking their toll on the GOP.
Republicans surrendered the Ohio seat once held by Bob Ney, who resigned after pleading guilty in a lobbying scandal, and the Florida seat of Mark Foley, who stepped down after the disclosure that he sent sexually explicit messages to male congressional pages.