WASHINGTON - Republicans toppled Senate Minority Leader Tom Daschle, winning their biggest Senate prize after sweeping through the South to enlarge the GOP majority.

Republicans were assured of 53 Senate seats after winning races Tuesday in Georgia, North Carolina, South Carolina and Louisiana - where the GOP won its first seat since Reconstruction.

Undecided races in Florida and Alaska will determine the final sweep of victory for Republicans, who currently have a 51-48 margin, plus a Democratic-leaning independent.

Daschle, who was labeled an obstructionist by Republicans, trailed former Rep. John Thune by more than 8,000 votes with 99 percent of the precincts reporting in South Dakota.

The last time a Senate leader was unseated was in 1952, when Barry Goldwater of Arizona turned Senate Majority Leader Ernest McFarland out of office.

"The nation spoke that we're on the right course, and we'll stay on that course and hopefully accelerate it," Senate Majority Leader Bill Frist, R-Tenn., said. The results showed voter rejection of Democratic "obstructionism" in the Senate, Frist said. He added that he expects the strengthened GOP majority will be called to confirm one or more Supreme Court nominees.

An Associated Press exit poll showed that South Dakota voters concerned with moral values and terrorism helped Thune.

Democrats had a nearly insurmountable hurdle to take control of the Senate, since most of the competitive races were in states where President Bush was strong. Several Democrats all but ran as independents in futile efforts to squeak through.

The stronger Republican Senate likely will mean more votes to confirm nominees to the Supreme Court in a second Bush term. One Republican winner, Sen. Arlen Specter of Pennsylvania, is in line to become chairman of the Senate Judiciary Committee, which holds confirmation hearings on court nominees.

In the South, Republican Rep. Johnny Isakson's easy victory in Georgia was expected, but Republican Reps. Jim DeMint in South Carolina and Richard Burr in North Carolina won more competitive races.

In Louisiana, Rep. David Vitter won an outright majority of more than 51 percent and avoided the runoff that under state law would have taken place Dec. 4 if he had not topped 50 percent.

Vitter had labeled his conservative Democratic opponent a "Washington liberal."

Democrats had reason to cheer in Illinois, where State Sen. Barack Obama easily won back a Republican seat. His victory wasn't a surprise, but will make the Democratic convention's keynote speaker the only black in the Senate next January.

The Democrats also will have the first Hispanic senator in more than a quarter century. Ken Salazar was narrowly elected in Colorado over Republican beer executive Pete Coors in a seat to replace the retiring Republican Sen. Ben Nighthorse Campbell.