The United States Senate is poised to pass a ban on workplace discrimination against gays and lesbians for the first time in American history, with 60 senators publicly committing to vote Monday for the Employment Non-Discrimination Act, or ENDA.

All 55 Democrats and five Republicans have said they will support the bill, reaching the 60-vote threshold needed to bypass a filibuster. A number of senators are taking significant political risks by voting for ENDA—the most notable of whom is a Democrat.

Sen. Mark Pryor (D-AR) may face the toughest reelection campaign of any incumbent senator in 2014. He’s running against conservative rising star Rep. Tom Cotton in culturally conservative Arkansas, a state that has become increasingly difficult for Democrats. Even a year out, polling has consistently showed the campaign in a dead heat.

But on October 29, the two-term senator came out in support of ENDA and said he would vote not just for cloture to bypass a filibuster but for the bill itself. The announcement was a big step for Pryor, one of two Democrats in the Senate who has yet to voice support for same-sex marriage. (The other is Sen. Joe Manchin of West Virginia.)

Pryor’s ENDA pledge came as a surprise to many advocates of the bill. “To be honest, none of us were really expecting to get Pryor,” one strategist involved in organizing support for the bill told The Daily Beast. And Fred Sainz, a spokesman for the Human Rights Campaign, hailed the senator for his “valiant move.”

Indeed, the Arkansas senator was the reason ENDA failed the last time it seemed close to passing the Senate, though not because he voted against it. Pryor’s father, David, served 18 years in the Senate and had supported ENDA when it was up for a vote in 1996. But the bill lost by one when David Pryor missed the vote after he was forced to fly back to Arkansas for his son Mark’s emergency cancer surgery.

This time around, Mark Pryor isn’t the only senator taking a political risk by supporting ENDA. Sen. Orrin Hatch (R-UT) represents a deeply conservative state and faced a Tea Party primary challenge in 2012 from those who felt he had “gone Washington.” Another Republican supporter, Lisa Murkowski (R-AK), lost her primary in 2010 and won reelection as a write-in that November. Although she’s taken more moderate votes since then, her support of ENDA will do her no favors in the Sarah Palin wing of the Alaska Republican Party. In addition to Hatch and Murkowski, two blue state Republicans, Sen. Susan Collins (R-ME) and Sen. Mark Kirk (R-IL), are supporting the bill.

But more Republicans were needed to overcome a filibuster. The magic 60th vote came on Monday morning from Nevada Republican Dean Heller, who announced his support as "the right thing to do." Republicans familiar with the effort say up to four more members of the GOP caucus could vote to end debate, including John McCain (R-AZ), Pat Toomey (R-PA), Kelly Ayotte (R-NH), and Rob Portman (R-OH). The support of McCain, the party’s presidential nominee in 2008, or Toomey, former president of the influential conservative advocacy group Club for Growth, would send a strong message to Republicans.

The biggest surprise among the Republicans lingering on the fence is Portman. The Ohio lawmaker has an openly gay son and was the first GOP senator to support same-sex marriage. Now he’s the only senator from either party to support gay marriage and not support ENDA. (Among the bill’s supporters, Pryor, Manchin, Collins, and Hatch are opposed to same-sex marriage.) While Portman has said he is leaning toward supporting the bill, he has yet to commit.

Presuming the bill clears the 60-vote hurdle on Monday, it will face a number of obstacles before becoming law. The first is the amendment process in the Senate, where pitfalls are possible around exemptions for religious institutions as well as ENDA’s prohibition against discrimination based on gender identity. But those should be far less difficult than the path ENDA faces in the House of Representatives.

In that Republican-controlled chamber, a majority of the members do not support the bill. That puts ENDA in a similar position to immigration reform, which passed the Senate in June but stalled in the House. Still, a ban on workplace discrimination against LGBT Americans polls better than a path to citizenship for undocumented immigrants, and the opposition is far less strident. About three-quarters of voters nationally support ENDA, and even in Mississippi, the state with the highest level of opposition, 63 percent of voters support it.

But despite such polling and an increasing number of major Republican donors in vocal support of ENDA, not to mention same-sex marriage, even a majority might not be enough in the House. After all, 218 members of Congress were willing to vote to end the government shutdown before it started, provided House Speaker John Boehner put “a clean continuing resolution” up for a vote. He just never did so.

Still, regardless of what happens in the House and whether the GOP leadership allows a vote on ENDA, the Senate’s vote will have political consequences. Pryor could alienate evangelical blue dog Democrats in Arkansas, and Republican supporters could invite primary challenges from social conservatives.

For his part, Sainz appeared more sanguine about the potential repercussions. Pointing to the polling, he suggested that supporting ENDA was politically wise. Rarely is voting for something with 70 percent approval considered risky, he noted.