Her family said she had died after a period of illness, reported the TT news agency on Thursday.
Lisbet Palme, a child psychologist, was chairwoman of Unicef in 1990-1991 and of the Swedish Unicef Committee until 1999. She was married to Olof Palme from 1956 until his death in 1986.
Mr Palme did not have a bodyguard with him on the night he and Mrs Palme were walking along the busy Sveavägen after a spontaneous trip to a downtown Stockholm cinema on February 28th, 1986.
A gunman came up from behind and shot him twice in the back. Mrs Palme was also grazed by a bullet. She later identified Christer Pettersson as the shooter in a line-up, but he was acquitted by an appeals court.
The murder sent shockwaves through Sweden and a killer was never convicted, nor was the gun found.
Mr and Mrs Palme had three children together, Mårten, Joakim and Mattias.
Lisbet Palme and Social Democrat Prime Minister Stefan Löfven in 2016. Photo: Henrik Montgomery/TT
Social Democrat leader and outgoing PM Stefan Löfven said he felt “great sorrow” at the news of Mrs Palme's death.
“I had many great conversations with Lisbeth Palme, most often in Gotland and in connection with speeches at Almedalen,” said Löfven in a statement, referring to the political festival founded by Mr Palme and often informally called 'Palmedalen'.
Löfven also highlighted Mrs Palme's long-term work with children's rights, including her role as chair of the Swedish Unicef Committee, and said that the best way to honour her memory was “to continue this work with as much energy as possible”.
Other politicians shared condolences on social media, including Foreign Minister Margot Wallström who paid tribute to “great, clever Lisbet” on Twitter.