The 80-year-old senator, a leading voice for his party on foreign policy, was pummeled for weeks by Republican rival Richard Mourdock for his breaches with conservative orthodoxy.
Among them: Lugar's support of citizenship for some illegal immigrants and his votes to confirm President Barack Obama's Supreme Court nominees, Sonia Sotomayor and Elena Kagan.
Lugar's defeat marks a triumph for the tea party in a campaign season otherwise shaping up as less favorable to a conservative insurgency than the 2010 election that swept many of the movement's candidates into office and fueled a Republican takeover of the House.
It also affirms the downside of Senate longevity at a time when voters, in Indiana as elsewhere, are in a surly mood over prolonged economic hardship. Lugar, a fixture of the Republican establishment in Washington since the 1970s, was poorly prepared to fight for survival.
"Lugar hasn't had a race in decades," said Jennifer Duffy, senior editor of the nonpartisan Cook Political Report. "Not years. Decades."
Indiana was one of four states holding elections Tuesday. In Wisconsin, voters were picking a Democrat to challenge Gov. Scott Walker next month in a recall spurred by the Republican incumbent's epic fight with organized labor.
Milwaukee Mayor Tom Barrett, the Democrat defeated by Walker in the 2010 governor's race, was favored to win a rematch. Labor's preferred Democrat, Kathleen Falk, was trailing in the polls.
In presidential primaries, Mitt Romney coasted to victory in Indiana and North Carolina and was expected to win West Virginia as well.
With a combined 107 delegates at stake on Tuesday, Romney remained short of the 1,144 needed to clinch the nomination, but he is likely to hit that milestone later this month.
For Lugar, the challenge mounted by Mourdock came as a rude surprise. A former chairman of the Senate Foreign Relations Committee, Lugar is one of the nation's most prominent advocates of arms control treaties. With former Sen. Sam Nunn, a Democrat, Lugar helped set up a program to secure and dismantle nuclear weapons in Russia, Ukraine, Belarus and other nations that were once part of the Soviet Union.
When he ran for president in 1996, Lugar stressed nuclear security. He quit the race after finishing seventh in the Iowa caucuses and fifth in the New Hampshire primary.
By and large, Lugar's voting record has been conservative, but he has often worked with Democrats -- a major liability this year in his re-election campaign. In 2005, Lugar and Obama, then a freshman senator, traveled together to Russia, Ukraine and Azerbaijan to inspect nuclear facilities. He and Obama later co-sponsored a measure expanding the Lugar-Nunn program to deactivate weapons and keep terrorists from acquiring them.
In his Senate campaign, Mourdock, 60, branded Lugar "Obama's favorite Republican."
In his own campaign ads, Mourdock portrayed Lugar as a Washington insider who had grown out of touch with Indiana.
"When Dick Lugar moved to Washington, he left behind more than his house," an announcer said in a Murdock TV ad. "He left behind his conservative Hoosier values."
In November's general election, Mourdock will run against Joe Donnelly, a Democratic congressman who would have faced a far tougher challenger in Lugar.
For Republicans, said Stuart Rothenberg, editor of the nonpartison Rothenberg Political Report, "I think it's harder to hold the seat with Mourdock, but I think they will hold the seat."
Republicans are hoping to win control of the Senate in November by maintaining control of the party's 47 seats and gaining four more.
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