The musical great, who had a history of heart problems, called police from his Florida home saying he was having trouble breathing, but emergency services were unable to resuscitate him and he was pronounced dead an hour later.
A statement on the Lynyrd Skynyrd website said: "Beloved pianist for the Lynyrd Skynyrd Band, Billy Powell, passed away last night. The family and band request your respect and understanding during this difficult time."
Billy was enrolled at Bishop Kenny High School and it was here that he met Leon Wilkeson, future bassist for Lynyrd Skynyrd and the pair soon became firm friends.
When he graduated in 1970, Billy did a brief spell in a community college, majoring in Music Theory, yet it was around the same time that he found work as a roadie for Lynyrd Skynyrd.
He remained working as a roadie for Skynyrd until 1972, when the band was hired to play the Bolles School prom. After setting up the band's equipment, Billy sat down at a piano in the corner of the room and began to play his own version of 'Free Bird'. Lead singer Ronnie Van Zant was so impressed, he invited Powell to join Lynyrd Skynyrd officially as their new keyboard player.
In 1973, Lynyrd Skynyrd got their first big break as they were signed to MCA Records and received national exposure with the release of their first album. Their success grew phenomenally with the release of their follow-up album, Second Helping, which featured their highest-charting single, "Sweet Home Alabama".
The band enjoyed great popularity over the next three years, culminating in the 1977 release of Street Survivors, which many considered to be their strongest effort to date. However, three days after the release of Street Survivors, Skynyrd's chartered plane crashed into a forest near McComb, Mississippi.
The crash took the lives of singer Ronnie Van Zant, guitarist Steve Gaines, his sister and backing vocalist Cassie Gaines, and assistant road manager Dean Kilpatrick. The remainder of the band suffered injuries ranging from mild to severe.
Powell suffered severe facial lacerations, almost completely losing his nose but was otherwise relatively uninjured. He was the first to be released from the hospital, and the only member able to attend the funerals of his fallen bandmates.
During the time between the plane crash and the Lynyrd Skynyrd reunion in 1987, Powell briefly joined a Christian rock band named Vision. His keyboard playing was often spotlighted in Vision concerts. Powell also spoke during the concerts about his newly found faith in Jesus Christ.
Powell rejoined Lynyrd Skynyrd in 1987 for a tribute tour, and remained with the band until his death. Guitarist Gary Rossington is the only member from the classic lineup who continues to record and perform with the reunited band today.
Van Zant said the band had recorded songs for an upcoming album and shows on Friday and Saturday night in the US have now been cancelled. The band are due to tour Europe, including concerts in London and Manchester, in May and June.