Chris Green, an officer from East Liverpool in Ohio, collapsed after handling the substance, believed to be Fentanyl.
The drug is a painkiller often used as a recreational drug, and is 50 to 100 times more powerful than fellow opioids morphine or heroin.
In fact, it is so potent it has been described as a “weapon of mass destruction”, as it can be absorbed into the body merely through skin contact.
The officer came into contact with the drug while searching a car on Friday night, after the driver completed an alleged drug deal.
While Mr Green had worn gloves and a mask during the search, a colleague noticed white powder on his shirt when he returned to the police station.
He instinctively brushed off the powder using a bare hand, and within minutes, he collapsed.
It took four doses of the opioid antidote, Narcan, to revive the officer – the first of which were administered by ambulance crews.
The officer took two days to recover.
Speaking to local newspaper The Morning Journal, he said: “I started talking weird. I slowly felt my body shutting down.
“I could hear them talking, but I couldn’t respond. I was in total shock. ‘No way I’m overdosing,’ I thought.”
The driver of the car, Justin Buckle, and his passenger, Cortez Collins, have been arrested and are facing charges of tampering with evidence.
Police say white powder was found all over the vehicle.
In recent years, several American states have been hit by a wave of Fentanyl-related deaths as part of an overdose epidemic across the country.
Its variant – Carfentanyl – is used on animals and can be 10,000 times more potent than morphine.
US singer Prince was found to have died from an accidental overdose of Fentanyl following his death last year.
During his last few months in the White House, former US president Barack Obama announced a £4.3m fund to tackle the illegal supply of the deadly drug.
Last month, West Yorkshire and Humberside police warned Class A drugs contaminated with Fentanyl and Carfentanyl could have made their way onto UK streets.