For the first time in the 16-year history of the list, Fortune examined the campaign contributions of the female executives at the top of the heap. When these women crack open their personal checkbooks for candidates, they favor Democrats over Republicans by a striking margin of more than two-to-one.

Indeed, the highest ranks of male and female corporate leaders are mirror opposites in the partisan split of their political contributions. The top ten most generous donors from the Most Powerful Women list have given more than $680,000 to Democrats over the last ten years — 68 percent of their total. The top ten male CEOs from the Fortune 500, on the other hand, forked over $642,000 to Republicans over that same time period — 67 percent of their overall giving.

The finding is all the more notable considering the environment: Heading into the homestretch of the midterm elections, Republicans are looking to seize power in the Senate and pad their House majority. To pull it off, the GOP has to limit its losses among women, traditionally a challenging demographic for the party. A leaked report from a pair of Republican outside groups recently sounded the alarm about the party’s standing with women, finding that female voters think Republicans are “intolerant” and stuck in the past.

Democratic candidates are eagerly pressing that same argument across the map, even as a new poll showed an opening for Republicans to cinch their gender gap with women. A Washington Post-ABC survey found approval of President Obama near all-time lows; it’s down from 55 to 44 percent with women, the poll found.

Against that backdrop, the apparent collective judgment by the country’s most successful women that Republicans don’t represent their best interest is sure to sting. But what to make of it?

The group’s partisan tilt is likely at least partly explained by their work. Most corporate political action committees, the accounts that companies use to hand out political contributions, hug the middle in their giving, with a slight edge toward Republicans. That’s because the companies prioritize support for incumbents from both parties to help open doors for their executives and lobbyists in Washington. Again, here, the men’s giving likely owes in part to their work: Four of the ten head companies in the oil and gas industry, which is bolder than most in showing its affinity for Republicans. The official giving by the companies in this group bears that out, with 64 of their PAC contributions going to GOP candidates.

But over the last ten years, the companies that employ the women on our list cut against the grain, favoring Democrats with 61 percent of the dollars they doled out from their corporate PACs. The women themselves — freer than their companies to express a clear partisan preference with their personal contributions — went even further, collectively directing 67 percent of their largesse to Democrats.

Two of the biggest givers on our women’s list help illustrate the phenomenon. Both hail from the tech industry, until recently inhospitable terrain for Republicans. And true to trend, neither leaves a doubt about her personal preferences: Yahoo (YHOO) CEO Marissa Mayer and Facebook (FB) COO Sheryl Sandberg both sent 99 percent of their contributions over the last ten years to Democrats — compared with their respective companies, which gave a comparatively moderate 76 percent and 72 percent to Dems. The similarities between the giving habits of Mayer and Sandberg don’t end there. Both delivered the bulk of their money through five-figure checks to party organizations rather than individual candidates (though they each gave $5,000 in direct cash to President Obama’s reelection bid). And both drew an exception to their exclusively Democratic giving to support one member of the GOP: the now-retired Sen. Olympia Snowe, a rarity as a female Republican in Congress and a champion of bipartisan compromise in an era increasingly hostile to it.

Women, broadly, have become a reliable source of funds for President Obama’s party — especially women with careers. Those with jobs outside the home were giving 62 percent of their contributions to Democrats at the start of this election cycle, a 2013 study by the Center for Responsive Politics found — up from 42 percent in the 1990 elections.

It’s a trend generally chalked up to economic considerations. Many of the women in that group are sole providers for their households, wary of the bottom falling out and therefore more receptive to Democratic appeals to protecting social safety net programs. So the revelation that women at the pinnacle of the economic ladder share the political inclinations — if not the same concerns — as those struggling on its lower rungs should confound some expectations.

“It’s fascinating,” says Debbie Walsh, director of the Center for American Women and Politics at Rutgers University. “I think there would be an assumption that women at that level would be as likely as their male counterparts in corporate America to give to the Republican Party. But in fact what you’re finding is that they are in line with women who work outside the home across the board.”