Wilson, 28, who on Monday was cleared by a grand jury investigating the shooting, had been a member of the city's police department for six years.
In a brief telephone interview, Wilson said he resigned after the police department told him it had received threats of violence if he remained an employee.
"I'm resigning of my own free will," he said. "I'm not willing to let someone else get hurt because of me."
He said resigning was "the hardest thing I've ever had to do.
"This is the only thing I've ever wanted to do."
Wilson's resignation letter reads:
"I, Darren Wilson, hereby resign my commission as a police officer with the City of Ferguson effective immediately. I have been told that my continued employment may put the residents and police officers of the City of Ferguson at risk, which is a circumstance that I cannot allow. For obvious reasons, I wanted to wait until the grand jury made their decision before I officially made my decision to resign. It was my hope to continue in police work, but the safety of other police officers and the community are of paramount importance to me. It is my hope that my resignation will allow the community to heal. I would like to thank all of my supporters and fellow officers throughout this process."
Neil Bruntrager, Wilson's attorney, said a news conference is being planned.
He said he acted without receiving a severance package, although he said more talks may be held.
The shooting of Brown, who was 18 and unarmed, sparked worldwide protests that continue this weekend. Wilson had been on paid administrative leave since the incident.
Protesters, including Brown's family members, have accused Wilson of murder in the incident and called for a special prosecutor to pursue charges against him.
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