When Gov. Ron DeSantis of Florida went to war against Disney over what he labels its “woke” corporate sensibility and its criticism of state policies, Tim Wildmon was cheering from the sidelines.

Mr. Wildmon, the president of the American Family Association, a right-wing religious organization, has more experience in this area than most: In 1995, his organization, which is known for its opposition to L.G.B.T.Q. rights, rallied a broad coalition of evangelical groups to boycott Disney after it extended family benefits to gay employees.

But since then, Mr. Wildmon has learned to temper his expectations. After an early wave of international media attention, the boycott receded from the headlines, and by the time Mr. Wildmon officially pulled the plug on it a decade later, it had had little discernible impact on Disney’s policies or revenues.

“It was very difficult to sustain for more than three or four years,” he said. “People move on. They lose interest. Things change.”

And some things stay the same. Almost 20 years later, Mr. DeSantis is trying to turn Americans against The Walt Disney Company, one of the most formidable superpowers of American popular culture and commerce. He has also joined the pile-on of another corporate-cultural behemoth, Anheuser-Busch InBev, which incurred a wave of outrage on the right this month over a Bud Light marketing campaign promoting a transgender influencer.

“I’d rather be governed by we the people rather than woke companies, so I believe pushback is in order across the board,” the governor said in a recent interview with Benny Johnson, a right-wing media personality.

Coming as he prepares to run for president, Mr. DeSantis’s moves are testing whether changes in Republican politics and in boardrooms have rewritten the rules for anti-corporate campaigns. American businesses are increasingly engaging in social debates, responding to consumer and employee demand. In the Republican Party, meanwhile, the party’s Trump-era populist rhetorical turn and hardening position on gender politics have combined to make corporate America an appealing battlefield for culture warriors.

But taking on Mickey Mouse remains a tricky business. As Mr. Wildmon and others can attest, brands of the scale and cultural footprint of Disney have emerged from past boycotts without much of a scratch. And corporations that might have been leery of such fights a generation ago are now more likely to see them as inevitable, and in some cases even a source of market advantage.

In Florida, Disney has proved a wily political foil for Mr. DeSantis. After the company criticized a Republican bill in the State Legislature limiting schools’ instruction on gender and sexuality last year, Mr. DeSantis tried to strip Disney of the unusual self-governance arrangement it has enjoyed for decades in the state. But his administration appeared to be outmaneuvered when Disney’s representatives found a workaround.

This month, the governor escalated the dispute by threatening a list of possible punishments. On Wednesday, after a board voted to void agreements that give the company control over expansion at its resort complex, Disney sued in federal court, claiming “a targeted campaign of government retaliation.”

Bryan Griffin, Mr. DeSantis’s press secretary, has described the company’s moves as “an attempt to subvert the will of the people of Florida.” Disney, one of the largest employers in the state, has repeatedly described its actions as compliant with state law. Its chief executive, Robert A. Iger, has criticized Mr. DeSantis’s actions as “anti-business” and “anti-Florida.”

Polls suggest Mr. DeSantis’s political success in the debate may hinge on whether he’s viewed as a populist reining in big business or a culture warrior. A Harvard-Harris poll this month found a majority of registered voters nationwide — and a vast majority of Republicans — siding with Mr. DeSantis in the showdown. The survey described Mr. DeSantis as attempting “to limit Disney’s autonomy” and remove “special tax status.”

But another poll, this one conducted this week by Reuters/Ipsos, found less than half of Republicans had a more favorable view of the governor because of his fight with Disney. And majorities of Democrats and Republicans said they were less likely to support a candidate who supported laws intended to punish companies for their positions on cultural issues.

The episode has been viewed as a weakness by his prospective rivals in the 2024 presidential primary field, in which polls show Mr. DeSantis has slipped. On his Truth Social platform, Donald J. Trump mocked Mr. DeSantis for being “absolutely destroyed by Disney.”

Chris Christie, the former governor of New Jersey, questioned whether Mr. DeSantis’s heavy-handed use of state power against the company undermined his claims of conservatism.

“Where are we headed here now that, if you express disagreement in this country, the government is now going to punish you?” Mr. Christie said at an event last week.

In the campaign against Anheuser-Busch, a more conventional boycott without the political complications of government intervention, the backlash has had a clearer impact. In recent days, amid reports of tumbling sales, the company announced that the marketing executives responsible for the promotional partnership with the influencer, Dylan Mulvaney, were on leave.

Other companies that have incurred the anger of consumers on the right and left, however, have generally found the ire to be short-lived. Nike was vilified by President Trump and others over its 2018 promotional campaign featuring the former N.F.L. quarterback Colin Kaepernick, who had faced outrage on the right for kneeling during the national anthem in protest of police shootings of unarmed Black people. Nike’s stock fell 3 percent after the company released its first Kaepernick ad, but within weeks it had rebounded to a record high.

Nike’s campaign was a signal moment in the shifting politics of corporate America, which has long made common cause with the Republican Party on issues like taxes and regulation but has been drawn into increasingly regular conflict with the party over social issues.

In part this is because corporations have become more socially liberal in their own policies, reflecting broader trends in public opinion on many issues. When the Human Rights Campaign, a prominent L.G.B.T.Q.-rights organization, published its first Corporate Equality Index in 2002, only 13 companies received the top score for L.G.B.T.Q.-friendliness. In 2022, 842 companies did.

“I think it’s something that’s important to their employees, to their customers and to their investors,” said Eric Bloem, the organization’s senior director for programs and corporate advocacy. “It’s all interrelated.”

In the 2010s, when newly Republican-controlled state legislatures began aggressively pursuing legislation targeting L.G.B.T.Q. rights, corporations’ new social politics came into direct conflict with their old Chamber of Commerce allegiances, and often outweighed them. Companies like PayPal, Deutsche Bank, Disney and Walmart canceled expansion plans, threatened boycotts and lobbied political leaders in several states over the new laws.

The business community’s shift accelerated after the police murder of George Floyd in 2020, which sent corporations as varied as Citigroup and McDonald’s scrambling to signal their solidarity with the emerging wave of racial justice protests.

Brands that have performed outreach to right-leaning Americans have been an exception rather than the rule, and they have been mostly smaller enterprises. But for Republican politicians like Mr. DeSantis, the party base’s discontent with the new corporate value-signaling has proved an opportunity. Last year, the communications firm Edelman found in its annual Trust Barometer survey that for the first time, a majority of Republican respondents — and more Republicans than Democrats — said they did not trust business.

“The Republican Party was all about promoting the virtues of capitalism,” said Vivek Ramaswamy, an entrepreneur and Republican presidential candidate who has centered a criticism of corporate America’s social liberalism in his campaign.

As recently as a few years ago, he said, campaigning against big business was an awkward fit for the party. Now, he said, “we can understand what’s happened a little better.”