'Lady Linda' passed away on Sunday morning at a hospital in Los Angeles, according to the singer's publicist.
Sir Tom Jones' wife, Lady Melinda Rose Woodward, has died following a "short but fierce" battle against cancer.
A statement posted on the singer's website said the 75-year-old had died on Sunday morning at Cedars Sinai Hospital in Los Angeles, surrounded by her husband and loved ones.
The singer had recently cancelled several shows due to "serious" family illness.
Sir Tom, 75, had been married to 'Lady Linda' since 1957. They have one son, Mark.
The couple were both children of coal miners in South Wales and became childhood sweethearts at the age of 15 before marrying a year later.
In his 2015 autobiography Over The Top And Back, the singer revealed the couple wanted more children but Lady Linda had been left infertile after a miscarriage.
In the same year, during an interview with American TV personality Larry King, Sir Tom addressed criticism about not including anything on his alleged affairs in the autobiography.
He said: "I don't think it's important. It's not what has made me. I've always looked at entertainers as 'why is that person where he or she is?'"
The Voice judge also told The Sunday Times magazine last year that his wife suffered from depression.
"I've realised she's had depression since she was young. She's always had a touch of it," he said.
"She's the most important thing in my life," Sir Tom said during the interview.
"An unbelievable woman. Linda is the love of my life and she still is, even though she doesn't look like she did. I don't look like I did, either, but I try my best."
Our sincere condolence to Tom Jones and family for the lost of their love one . RIP 'Lady Linda' ..... The PICs