For Tom Donohue, failure is not an option as Congress faces a tight political window to pass President Trump’s signature trade deal with Canada and Mexico.

Mr. Donohue, the longtime head of the U.S. Chamber of Commerce, the nation’s biggest business lobby, on Thursday called the updated NAFTA accord — dubbed the U.S.-Mexico-Canada Agreement — is the Chamber’s “top policy priority,” a “$4 billion a day trade deal” so important he brushes off questions of what happens if the deal is rejected.

“Walking away from the USMCA at this time would not only be a serious economic failure, it would be a very, very devastating political problem,” Mr. Donohue told reporters Thursday at a rally for the free-trade deal at the Chamber’s Washington headquarters just a block from the White House.

With the August recess at hand and a short fall legislating window on Capitol Hill, members of the Chamber are picking up the pace, targeting key districts and working with both Republicans and Democrats to ensure the agreement’s ratification by the end of September. Treaty backers are cautiously optimistic, but the tight timing, the partisan atmosphere entering an election year, and the reluctance of Democrats to hand President Trump a major policy victory are all clouding the forecasts.

The new NAFTA deal, the first major overhaul since it was came into effect in 1995, was signed in November and still must be ratified by Washington and Ottawa. Chamber officials said they will be meeting with lawmakers daily and holding educational rallies around the country, particularly in key agricultural areas of the Midwest.

“The rest of the world is moving forward with new trade agreements, which puts us at risk of falling behind,” said John Bode, president and CEO of Corn Refiners Association. “If Congress fails to approve, it will be very hard to negotiate new agreements with other countries.”

More than 600 companies, organizations and chambers submitted a letter to Congress this week expressing “wide and deep” support for the USMCA, which updates key provisions of the original deal in fields such as auto production, labor and environmental standards and the digital economy.

U.S. officials say the deal will open up Canada’s dairy market to U.S. farmers, a key goal for International Dairy Foods Association President and CEO Michael Dykes. While there is a lot of bipartisan support for the deal, he cautioned that there are also many new members of Congress who have never voted on a trade agreement.

While Mr. Donohue insisted that the USMCA has “ever growing support on both sides,” some Republicans fear congressional Democrats will be reluctant to ratify the agreement with an eye on the 2020 election. President Trump was a fierce critic of the original NAFTA deal and the USMCA would be the biggest new trade deal of his presidency.

“I predict [the USMCA] will pass with flying colors in the Senate, and it will pass with flying colors in the House, too — if [Democratic Speaker Nancy] Pelosi allows it to come to the floor,” Sen. Mike Braun, Indiana Republican, told Bloomberg News on Thursday. “Regrettably, it’s being slow-walked in the House for political reasons.”

Mr. Donohue said the Chamber was ready to provide political cover for an congressional Democrats who come under fire for supporting the agreement.

He said if a vulnerable candidate up for reelection is attacked for ratifying the agreement, the chamber would in “enormous ways refute the attack.”

President Trump and his aides are stepping up their own lobbying campaign to win support on Capitol Hill. Vice President Mike Pence traveled to Iowa on Tuesday to talk up the benefits of the revised NAFTA deal.

Despite the tricky politics of trade, “I think the USMCA will actually happen,” said Mr. Braun. “I just think it’s silly the way we’re doing it.”

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