The Department of Homeland Security described the vehicle's passenger as "a Venezuelan illegal alien affiliated with the transnational Tren de Aragua prostitution ring" who had been involved in a recent shooting in Portland.
When agents identified themselves to the occupants during a "targeted vehicle stop" in the city on Thursday afternoon, the driver tried to run them over, the department said in a written statement.
"Fearing for his life and safety, an agent fired a defensive shot," the statement said. "The driver drove off with the passenger, fleeing the scene."
There was no immediate independent corroboration of that account or of any gang affiliation of the vehicle's occupants.
During prior shootings involving agents involved in President Donald Trump's surge of immigration enforcement in US cities, including Wednesday's shooting by an Immigration and Customs Enforcement officer in Minneapolis, video evidence cast doubt on the administration's descriptions of what prompted the shootings.
Trump and his allies have consistently blamed Tren de Aragua for being at the root of the violence and illicit drug dealing that plague some US cities.
The shooting escalates tensions in a city that has long had a contentious relationship with President Donald Trump, whose decision to send militarised personnel into US cities to conduct immigration enforcement drew long-running nightly protests outside the ICE building in Portland.
Their conditions were not immediately known. Portland Police Chief Bob Day said the FBI was leading the investigation and that he had no details about the events that led to the shooting.
Portland Mayor Keith Wilson and the city council called on US Immigration and Customs Enforcement to end all operations in Oregon's largest city until a full investigation is completed.
Wilson also suggested at a news conference that he didn't necessarily believe the federal government's account of the shooting: "There was a time we could take them at their word. That time is long past."
The shooting comes a day after an Immigration and Customs Enforcement (ICE) officer shot and killed a woman in Minnesota.
Minneapolis woman Renee Nicole Good, 37, was shot by an ICE officer as she tried to drive away on a snowy Minneapolis street on Wednesday.
The killing has inflamed tensions in the community and is causing friction between state and federal authorities over its investigation.
US President Donald Trump has made a wide-ranging crackdown on crime and immigration in Democratic cities a centrepiece of his second term in office.
He has deployed federal law enforcement officials and National Guard troops to support the operations and has floated the idea of invoking the Insurrection Act to try to stop his opponents from blocking his plans through the courts.
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