Woodward passed away at Cedars-Sinai hospital in Los Angeles, a statement read. She was believed to have been 75, reported The Guardian.
She was surrounded by her husband and family who "have asked for privacy at this difficult time," added the statement.
Jones had been married to Lady Woodward for 59 years. The pair had known each other from childhood and began dating at 15. She opted to stay out of the limelight when her husband first found fame in 1965, with hit song "It's Not Unusual".
In his autobiography, Jones described how he first fell for Woodward after seeing her at school when they were both 12, living in the Welsh town of Treforest, Pontypridd.
More From This Section
The pair married in 1957 shortly after her 16th birthday. Writing in his autobiography, Jones said he had "never had that feeling for anyone else... I don't think you can fall in love more than once."
Jones had, however, admitted he had been unfaithful several times.
Woodward had suffered two previous cancer scares.
Woodward did not travel with her husband on his world tours or even come to Buckingham Palace when Jones collected his knighthood in 2006.
She also stayed back in LA when Jones began filming as a judge on BBC talent contest The Voice in 2012.
The couple has one son, Mark, 59, who also acts as the singer's manager.