His representatives confirmed the guitarist, 70, died in a Zurich hotel room on Wednesday.
Winter's last performance was on Saturday at the Lovely Days Festival in Austria.
The popular musician was known for his work with Muddy Waters and Rolling Stone named him one of the 100 greatest guitarists of all time.
"Texas blues icon Johnny Winter has passed away on July 16, 2014 in his hotel room in Zurich, Switzerland," reads a post on his Facebook page. "His wife, family and bandmates are all saddened by the loss of their loved one and one of the world's finest guitarists."
Winter, a native of Beaumont, Texas, is the older brother of musician Edgar Winter.
RIP - legendary blues guitarist Johnny Winter pic.twitter.com/ltBIqRgIgq— Gibson Guitar UK (@GibsonGuitarUK) July 17, 2014