Perkins was having chest pains when he went to take a nap and paramedics could not revive him, said Hugh Southard, Perkins' agent for the last 15 years.
The piano man played with an aggressive style and sang with a distinctive gravelly voice.
He accompanied Sonny Boy Williamson on the popular King Biscuit Time radio show broadcast on KFFA in Helena, Ark., in the 1940s. He toured with Ike Turner in the 1950s and joined Waters' band in 1969.
"He is the blues, he is the epitome of it," Southard said. "He lived it, breathed it."
Perkins won a Grammy in February for best traditional blues album for "Joined at the Hip: Pinetop Perkins & Willie "Big Eyes" Smith." That win made Perkins the oldest Grammy winner, edging out late comedian George Burns, who was 95 when he won in the spoken category for "Gracie: A Love Story" in 1990.
Perkins also won a 2007 Grammy for best traditional blues album for his collaboration on the "Last of the Great Mississippi Delta Bluesmen: Live in Dallas." He also received a lifetime achievement Grammy in 2005.
Even at his age, he was a regular fixture at Austin blues clubs, playing regular gigs up to last month. He had more than 20 performances booked this year, Southard said. After they won the Grammy this year, Smith and Perkins discussed recording another CD.
Perkins was born in Belzoni, Miss., in 1913 and was believed to be the oldest of the old-time Delta blues musicians still performing.
In an 80-year career, he played at juke joints, nightclubs and festivals. He didn't start recording in his own name until he was in his 70s and released more than 15 solo records since 1992.
That drive to keep playing the blues kept is what kept him alive, Southard said.
Perkins also loved fast food and was a smoker until the day he died.
"Two cheeseburgers, apple pie, a cigarette and a pretty girl was all he wanted," Southard said.
Perkins, who had no survivors, will be buried in his hometown, Southard said, but details were not immediately available. An Austin tribute will be planned to honor his life and music will be scheduled within the next week, Southard said.
He moved to Austin in 2004 to live with an associate since he had no family.