The ex-Labour culture secretary, who had been diagnosed with a brain tumour in May last year, suffered a haemorrhage on Friday.
She had been in a coma until her death on Saturday.
Baroness Jowell was a popular figure in Parliament who played a major role in securing the 2012 Olympics for London when she led the culture department.
In recent months, she moved fellow peers in the House of Lords to tears as she discussed her condition and called for patients to have better access to experimental treatment.
A family spokesman said: “It is with great sadness, and an enormous sense of loss, that we announce the death of Tessa Jowell.
“She died peacefully at the family home near Shipston-on-Stour in Warwickshire last night, shortly after 10pm.
“Her husband David and their children Jessie and Matthew were by her side, with Jessie’s husband Finn, Matthew’s wife Ella, and David’s children from his first marriage.”
The spokesman added: “In addition to chemotherapy and radiotherapy, in recent months doctors tried innovative new treatments which Tessa gladly embraced, but sadly the tumour recently progressed very quickly.”
Former prime minister Tony Blair said: “Tessa had passion, determination and simple human decency in greater measure than any person I have ever known.”
Lord Sebastian Coe, president of the IAAF and former chairman of the London organising committee of the Olympics, said: “Tessa was not just a close friend, she was a life enhancer.
“Her contribution to the Olympic and Paralympic Games is easily defined – quite simply, without Tessa there would have been no London 2012, and without Tessa they would not have been the success they were.”
Baroness Jowell became MP for the south London Dulwich and West Norwood constituency in 1992.
After Labour’s landslide election victory five years later, she held a succession of ministerial jobs, including employment minister and minister for women, before joining the Cabinet as culture secretary in 2001.
She took on the job of convincing unsure colleagues about the merits of hosting the Olympics in 2012. London finally won the vote in July 2005.
In 2012 she was made Dame Tessa Jowell in the Queen’s Birthday Honours for political and charitable services, which were partly in recognition of her work on the Olympics.
Three years later, after stepping down from the Commons at the 2015 general election, she was made Baroness Jowell of Brixton.
She later stood to be Labour’s candidate for mayor of London in 2016 but lost out to Sadiq Khan.