Her and Lennon's son Julian, also a singer and songwriter, paid a tribute to his mother on his website.
"Cynthia Lennon passed away today at her home in Mallorca, Spain following a short but brave battle with cancer. Her son Julian Lennon was at her bedside throughout. The family are thankful for your prayers. Please respect their privacy at this difficult time," read the message.
Cynthia met Lennon at the Liverpool College of Art in the late 1950s and the two began dating. She fell pregnant in 1962 and the couple tied the knot in August while the band was still to become famous.
The couple divorced in 1968 after Cynthia discovered her husband's affair with Japanese artist Yoko Ono. Cynthia wrote two memoirs about her time with Lennon.
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She later went on to marry three more times.
Paying tribute to Cynthia, former Beatle Paul McCartney said, "The news of Cynthia's passing is very sad. She was a lovely lady who I've known since our early days together in Liverpool. She was a good mother to Julian and will be missed by us all, but I will always have great memories of our times together."
"Peace and love to Julian Lennon God bless Cynthia love Ringo and Barbara xx," tweeted Ringo Starr.