In Delaware's closed primary, in which only registered Republicans could vote, O'Donnell - a marketing consultant who's had very few clients in recent years - defeated Castle last night with about 53 percent of the vote compared with roughly 47 percent for Castle, who was governor before serving 18 years in Congress.
"I think this is a signature primary, a kind of a bellwether," said G. Terry Madonna, a Franklin and Marshall political scientist and pollster. He said that right-wing Republicans had succeeded in "nationalizing elections like the one in Delaware, where anger at Obama mattered more than Castle's familiarity.
O'Donnell's upset - aided by the endorsements of Sarah Palin, South Carolina Sen. Jim DeMint and the Tea Party Express in the race's waning days - also creates a huge problem for national Republicans who were hopeful of retaking the Senate and the House in November.
The National Republican Senatorial Committee said last night that it doesn't plan to spend money on O'Donnell's campaign, the Wall Street Journal reported. An NRSC official said that could change if her position improves.
Polling in Delaware has shown that Castle - always a big vote-getter from independents and Democrats - would have been likely to defeat the Democratic nominee, Chris Coons, New Castle County executive.
But those same surveys show O'Donnell, whose appeal is largely to conservatives - thanks in part to a history of controversial statements about touchy issues like abstinence, pornography and even masturbation - losing to Coons by double digits.
Last night was the final flurry of primaries going into the fall general election, and the Delaware showdown was just one of several key races in which ultraconservatives were on the warpath against GOP-backed moderates.
In the New York governor's contest, well-known Republican stalwart Rick Lazio was defeated by tea-party-backed rival Carl Paladino, a construction executive.
Remarkably, Paladino's rapid rise in the polls was not halted by reports that he forwarded racist e-mails - one called "Obama Inauguration Rehearsal" showed dancing African tribesmen - and pornographic ones. That punctuated a year in which nothing seems to trump voter anger at insider candidates.
"Voters are registering their discontent with the status quo," said Costas Panagopoulos, editor of Campaigns & Elections and director of the Center for Electoral Politics and Democracy, at Fordham University. That is happening in both parties, he noted, adding that "the types of people who vote in primaries tend to be more extreme and more ideological."
Meanwhile, in New Hampshire, the GOP-establishment candidate there - former state Attorney General Kelly Ayotte, who surprised some experts by gaining Palin's endorsement - was running neck-and-neck early this morning with Ovide Lamontagne, a conservative challenger endorsed by tea-party groups.
In Delaware, wary GOP officials - reeling from last month's primary upset of incumbent Sen. Lisa Murkowski in Alaska - launched a furious last-minute offensive to portray O'Donnell as too immature for the Senate and bogged down by money and tax woes.
Yesterday, the state was blitzed with robocalls from a campaign manager for O'Donnell's 2008 Senate campaign against now- Vice President Joe Biden, who in the recorded message described the tea-party darling as "a complete fraud."
There were some key primaries for Democrats last night, too - especially in New York, where 40-year Harlem congressman Charlie Rangel - facing House ethics charges - beat back a spirited challenge from Adam Clayton Powell IV.