Preston’s death comes just over a decade after the couple lost their son Jett.
Travolta announced Kelly's death on his Instagram, saying he would be “taking some time to be there for my children who have lost their mother.”
He continued: “Please know that I will feel your outpouring of love in the weeks and months ahead as we heal.”
Kelly’s breast cancer battle
Jerry Maguire actress Kelly Preston, 57, had been battling breast cancer for two years, choosing to keep her diagnosis private.
According to People magazine, the What a Girl Wants star had been undergoing medical treatment for breast cancer for “some time”.
"On the morning of July 12, 2020, Kelly Preston, adored wife and mother, passed away following a two-year battle with breast cancer," a family representative told People.
"Choosing to keep her fight private, she had been undergoing medical treatment for some time, supported by her closest family and friends," they said.
"She was a bright, beautiful and loving soul who cared deeply about others and who brought life to everything she touched.
“Her family asks for your understanding of their need for privacy at this time."
Travolta thanked the care staff at MD Anderson Cancer Centre in his Instagram announcement.
“[Kelly] fought a courageous fight with the love and support of so many,” he wrote.
“My family and I will forever be grateful to her doctors and nurses at MD Anderson Cancer Center, all the medical centers that have helped, as well as her many friends and loved ones who have been by her side. Kelly’s love and life will always be remembered.”
It is with a very heavy heart that I inform you that my beautiful wife Kelly has lost her two-year battle with breast cancer. She fought a courageous fight with the love and support of so many. My family and I will forever be grateful to her doctors and nurses at MD Anderson Cancer Center, all the medical centers that have helped, as well as her many friends and loved ones who have been by her side. Kelly’s love and life will always be remembered. I will be taking some time to be there for my children who have lost their mother, so forgive me in advance if you don’t hear from us for a while. But please know that I will feel your outpouring of love in the weeks and months ahead as we heal. All my love, JT
A post shared by John Travolta (@johntravolta) on Jul 12, 2020 at 10:20pm PDT
The pair met in 1987 on the set of The Experts and married in 1991.
It is tragically the second time Travolta has lost a loved one to cancer. In 1976, he began a relationship with actress Diana Hyland after meeting her on the set of TV movie, The Boy in the Plastic Bubble.
They remained together until Hyland's death from breast cancer in March 1977.
The tragic death of John and Kelly’s son Jett
Jett Travolta, born in 1992, suffered from Kawasaki disease as an infant and had a history of seizures.
On January 2, 2009, while their family were on holiday in the Bahamas, Jett tragically passed away at the age of 16.
In a statement posted to John Travolta’s website, Travolta and Preston said he had knocked his head on a bathtub during a seizure.
"Jett was the most wonderful son that two parents could ever ask for and lit up the lives of everyone he encountered," the statement read.
"We are heartbroken that our time with him was so brief. We will cherish the time we had with him for the rest of our lives."
Travolta has two more children with Preston: Ella Bleu (born 2000) and Benjamin (born 2010).