The Wisconsin Democrat faces a wealthy political newcomer with early backing from tea party activists in a state that has many independent voters and is known for doing its own thing.
Likely GOP nominee Ron Johnson is running an outsider's campaign in a year that seems to favor outsiders.
"We have to boot professional politicians out of Washington," he says in his first campaign ad.
Feingold, now in his third term, knows he has a fight on his hands. Never shy about showcasing his independent streak, he reiterated his splits with the White House and fellow Democrats on two key policies last week.
"Regardless of who is in command, the president's current strategy in Afghanistan is counterproductive," Feingold said as the Senate confirmed Gen. David Petraeus to lead that war.
Feingold also renewed his opposition to the regulatory overhaul that Obama and Democrats wrote for Wall Street. "My test for the financial regulatory reform bill is whether it will prevent another crisis," and the measure "fails that test," he said.
And in one of his first campaign ads, Feingold recalls his opposition to the unpopular 2008 rescue of banks and other financial institutions, a measure supported by many Democrats, including Obama. "I said 'No' to the bailout," he says.
His occasional breaks from party orthodoxy could be his key to political survival in a campaign season that's already claimed five congressional incumbents and several establishment-backed candidates.
But, as Republicans are quick to remind voters, Feingold also backed Obama's economic stimulus plan and health care overhaul.
Four months before November, public and private surveys show a surprisingly tight race - underscoring why the GOP is hopeful and Democrats are anxious about their Senate prospects in the first midterm congressional elections of Obama's presidency.
Democrats started the election year anticipating that several Senate incumbents would be vulnerable, including Majority Leader Harry Reid in Nevada, Blanche Lincoln in Arkansas and Michael Bennet in Colorado.
But few expected Feingold, Barbara Boxer in California or Patty Murray in Washington to confront serious challenges. All three face competitive contests.
Republican victories in any or all of the three races would indicate a huge night for the GOP, perhaps big enough to take control of Senate. To do it, they must claim 10 seats from Democrats without losing any of their own - a tall order.
At the least, more competitive races mean Democrats will have to spend money in places they didn't think they needed it. That could mean less money for persuading and motivating voters in other must-win states.
Senate Republicans lag in overall fundraising. But they are buoyed by having several deep-pocketed GOP candidates, like Johnson and Boxer's opponent, former Hewlett-Packard CEO Carly Fiorina.
Democrats don't dispute that Republicans have succeeded in putting more Senate seats in play, including Feingold's.
But they argue that the GOP won't succeed in Wisconsin because, like Sharron Angle in Nevada and Rand Paul in Kentucky, Johnson is a far-right candidate who could have a problem attracting swing voters. Democrats say they'd rather Feingold face Johnson, a conservative who has never run statewide, than the more moderate former Wisconsin Gov. Tommy Thompson, who declined overtures to run.
Feingold has 18 years in the Senate and a strong base of supporters as well as a record as an aggressive campaigner and prolific fundraiser. He had raised $11.3 million and had $4.3 million on hand as of March, the most recent figures available, and recently got help from Vice President Joe Biden. Nonetheless, one of Feingold's strategists, John Krauss, casts the senator as the underdog in the race.
Johnson, owner of a Wisconsin-based company that makes plastic packaging materials, has a personal fortune and has suggested he will spend as much as $15 million on the race. He already has run $1 million worth of ads, and is counting on support from people tired of Feingold.
The Republican seemingly came out of nowhere when he won the state GOP convention - and the party endorsement - just days after getting in the race. He all but cleared the primary field. Only businessman Dave Westlake, a long shot in the September primary, remains.
Johnson won over tea party activists early, but that support has waned in recent weeks after the GOP establishment embraced him.
In conservative fashion, he calls for reducing spending by reducing the size of government and opposes "blanket amnesty" for illegal immigrants as well as cap-and-trade legislation to address climate change: "I do not believe man-made global warming is proven."
He advocates repealing the health care overhaul, calling it "the greatest assault on our freedom in my lifetime."
Johnson has suggested that the Second Amendment right to bear arms was intended "so we could keep government in check." He's called shutting down the IRS "a wonderful thing," though questioned the practicality of it. And he has wondered how "Social Security is different from a giant Ponzi scheme."
Democrats say those remarks illustrate that Johnson is outside the mainstream.