Should the Democrats take 60 seats in the senate it would make it nearly impossible for the opposition Republicans to use a filibuster to kill legislation.
A filibuster, a procedural way to extend debate indefinitely and keep a proposal from coming to a vote, can be cut off in the senate with a "supermajority" of 60 votes.
The Democrats ousted two incumbent Republican senators and picked up two seats held by retiring Republican senators in Virginia and New Mexico.
In a major upset for the Republicans, Kay Hagan, a Democratic state legislator, unseated incumbent senator Elizabeth Dole, a former cabinet secretary and one of the biggest names in the Republican Party.
Dole had been criticised for spending little time in recent years in North Carolina.
In Virginia, Mark Warner, a former Democratic governor, breezed to victory over Republican Jim Gilmore, another former governor, in the race to replace Senator John Warner, the retiring Republican incumbent.
The two Warners are not related.
In New Mexico, Democrat Tom Udall, the son of former long-term congressman Stewart Udall, defeated a Republican challenger to win the seat being vacated by Pete Domenici, another retiring Republican senator.
In New Hampshire, Republican Senator John Sununu lost to Democrat Jeanne Shaheen - who has refered to Sununu as Bush's "evil twin".
Other Democratic winners included Joe Biden, Barack Obama's vice-presidential candidate and a Delaware senator. Biden is expected to relinquish his seat.
According to other preliminary counts, nine Democrats and eight Republicans retained their seats.
Among the Republican survivors was Senator Mitch McConnell of Kentucky, who outpolled Bruce Lunsford, a millionaire businessman Democrat, to retain his seat.
McConnell, the senate minority leader, has been heralded as a master strategist and could continue to be a thorn in the side of the Democrats.
The senate Republican campaign committee warned in an advertisement last week that liberals threatened to take total control of Washington.
"No checks. No balances ... a liberal agenda so scary its effects will be felt for a generation," the advert said.
But a final pre-election poll by Gallup - taken at the beginning of the November - indicated that American voters generally favour Democrats in Congress by about 53 per cent to 41 per cent.
In the House of Representatives, the Democrats extended their control, unseating 10 Republican incumbents and capitalising on the departures of 29 Republican Representatives.
Republicans were only able to knock off four Democratic incumbents.
Final results showed the Democrats had won 258 seats, while the Republicans had won 177.