Williams, 54, was found dead by family members at his penthouse apartment in Brooklyn, New York, last September.

New York City's medical examiner ruled he had died of acute drug intoxication.

US Attorney Damian Williams and New York City Police Commissioner Keechant Sewell have said the four men were charged in Manhattan federal court over a narcotics conspiracy alleging the distribution of heroin laced with fentanyl, resulting in the actor's death.

Williams, who had been nominated for multiple Emmy awards, was best known for playing the gun-carrying drug dealer Omar Little in the HBO crime drama.

All four were arrested on Tuesday and were being held in custody, including one defendant who was arrested in Puerto Rico.

The US attorney said the crimes and charges were the result of a "public health crisis".

"And it has to stop. Deadly opioids like fentanyl and heroin don't care about who you are or what you've accomplished. They just feed addiction and lead to tragedy," the prosecutor said.

Ms Sewell said police detectives in Brooklyn "lived this case, never relenting in their investigation until they could bring a measure of justice to Michael K Williams and his family".

'Make believe he got shot'

Court papers say Williams' death on 6 September 2021 resulted from drugs sold by a drug trafficking organisation that has operated since at least August 2020 in Brooklyn's Williamsburg neighbourhood.

Screenshots from surveillance video contained in the court papers included one in which defendant Irvin Cartagena can be seen executing the hand-to-hand transaction, authorities said.

Officials also say the men continued to sell fentanyl-laced heroin in broad daylight amid apartment buildings in Brooklyn and Manhattan even after learning that Williams had died from one of their products.

Deputy Chief John Chell previously said he had instructed his detectives in north Brooklyn to treat the death as a homicide.

"Treat this case as if Michael K Williams was hit by a bullet," Mr Chell told the Daily Beast he remembers telling the detectives.

"Make believe he got shot."