According to a statement, Woodfox, who was facing a third trial for the 1972 killing of prison guard Brent Miller, pleaded no contest Friday to lesser charges.
"Although I was looking forward to proving my innocence at a new trial, concerns about my health and my age have caused me to resolve this case," he said.
Woodfox thanked his brother, Michel, and the other two members of the "Angola 3."
Woodfox had spent more than four decades in solitary confinement after being convicted for Miller's killing at the Louisiana State Penitentiary at Angola.
A federal appeals court overturned Woodfox's conviction in 2014 -- the second time it had been overturned -- but he had remained behind bars during the appeals process.
Woodfox and Herman Wallace were convicted in 1973 of killing Miller. A third inmate, Robert King, was linked to Miller's death, but never charged.
The group became known as the "Angola 3," and the case has been a cause celebre for years, with activists arguing there is no evidence tying the three men to the crime and decrying the decades they each spent in solitary confinement.
Samuel D'Aquilla, district attorney for Louisiana's West Feliciana Parish, told CNN that he was "not really in agreement" with the decision to release Albert Woodfox, but said "it was probably the best thing to do," given the difficulties posed by a new trial.
"A lot of the witnesses (from Woodfox's 1973 murder trial) are now dead," he said. "I'd like to say for the record, he is a murderer. He was convicted twice by juries and those convictions were overturned both times on technicalities."
Human rights organization Amnesty International celebrated his release, which comes on his 69th birthday.
"After four decades of isolation, Albert Woodfox's release is long overdue and undeniably just," Jasmine Heiss, the senior campaigner at Amnesty International USA's Individuals and Risk Campaign. "Nothing will truly repair the cruel, inhuman and degrading solitary confinement that the state of Louisiana inflicted upon him."
Woodfox -- who was originally imprisoned on an armed robbery conviction -- has said he had tried to point out injustices at the prison, including instances of segregation, corruption and rape, and was targeted and wrongfully accused because of his activism as a Black Panther.
King was freed after his conviction in the killing of a fellow inmate was overturned in 2001.
The same went for Herman Wallace, who was released in 2013 after a judge vacated his murder conviction and sentence. He only experienced a few days of freedom; he was suffering from terminal liver cancer and died just days later.
The Angola 3 case spurred the creation of the International Coalition to Free the Angola 3 and drew the United Nations into the fray. Several U.S. lawmakers have pointed to the case as a sign that reforms are needed in Louisiana's prison system. Even Teenie Rogers, the widow of slain prison guard Miller, has said she thinks the men are innocent.
Their plight has also spawned at least three documentaries, including "Angola 3: Black Panthers and the Last Slave Plantation," "Herman's House" and "In the Land of the Free... ," narrated by actor Samuel L. Jackson.