Okonjo-Iweala, who formerly held the No. 2 post at the World Bank, had amassed wide support among African countries and secured around 80 votes, or half of the organization's members, by mid-October. More recently, she gained the backing of the 27 European Union members, all but clinching victory.
But the meeting of members on Wednesday failed to finalize the selection -- a race between Okonjo-Iweala and South Korean Trade Minister Yoo Myung-hee -- due to Washington's rejection.
"One delegation could not support the candidacy of Dr. Ngozi and said they would continue to support South Korean minister Yoo. That delegation was the United States of America," WTO spokesman Keith Rockwell told reporters at the group's headquarters in Geneva after the closed-door meeting.
The WTO's decision-making process is based on consensus, and either candidate will need to win the blessing of all 164 members.
According to a person with knowledge of the matter, members including Japan spoke up in favor of concluding the process with Okonjo-Iweala as the appointee.
Despite U.S. resistance, a spokesperson for Okonjo-Iweala's campaign said the candidate is "immensely humbled to receive the backing of the WTO's selection committee" and "looks forward to the General Council on Nov. 9 when the committee will recommend her appointment as Director-General."
"A swift conclusion to the process will allow members to begin again to work, together, on the urgent challenges and priorities," the campaign spokesperson said.
The opposition is reminiscent of the skepticism by President Donald Trump's administration toward the World Health Organization, which is led by Director-General Tedros Adhanom Ghebreyesus, a former Ethiopian foreign minister. The White House repeatedly criticized Tedros as being pro-China and ultimately announced a U.S. withdrawal from the WHO due to the group's "alarming lack of independence" from China.
Like Ethiopia, Nigeria is a heavy recipient of Chinese economic aid. But Okonjo-Iweala has lived many years in the Washington suburbs due to her 25-year career at the World Bank.
The Harvard-educated Okonjo-Iweala obtained American citizenship in 2019 and has dual nationality with Nigeria. She was nominated to the top WTO job by her native African country.
Washington's opposition creates a tricky situation for its ally Japan. Tokyo had been wary of Okonjo-Iweala's rival candidate, fearing that a Yoo-led WTO may rule in favor of South Korea in its many trade disputes with Japan.
Either Okonjo-Iweala or Yoo would be the first woman to lead the Geneva-based trade body.
The new chief will be thrust immediately into the U.S.-China tug of war over the future of the organization. Predecessor Roberto Azevedo, a Brazilian, stepped down with a year left in his term as WTO reforms stalled.
The organization also is coping with a crippled dispute settlement system after the U.S. blocked the appointment of several judges to its Appellate Body, accusing the court of overreaching and over-interpreting WTO agreements.
The new director-general also will have to mitigate growing complaints, led by Washington, of China's simultaneous inclusion in the global trade system and its use of state subsidies.
During an interview with Nikkei Asia in July, Okonjo-Iweala said "it's important to listen to who feels it's not fair and then restore that balance of rights and obligations that members need to undertake."
The World Bank veteran described herself as a reformer and said she has strong political and negotiation skills.
"I'm a good listener, and you need listening skills to make this work," she said. "I'm pragmatic, and I'm solutions oriented."
Okonjo-Iweala's experience as chair of the Global Alliance for Vaccines and Immunization, a Geneva-based public-private partnership aimed at increasing access to immunization in poor countries, will help guide one of her first tasks: facilitating a trade mechanism for COVID-19 vaccines.
The economist, who also sits on the board of Twitter, cited in her interview with Nikkei an urgency to update the WTO's rulebook to address new challenges such as digital trade. But such negotiations, when the organization is in pressing need of structural reforms, likely will take a long time to bear fruit.