The prime minister's mother, Charlotte Johnson Wahl, has died aged 79.
A notice published in the Times newspaper said she died "suddenly and peacefully" at St Mary's Hospital in west London.
Boris Johnson once described his mother, who was a painter, as the "supreme authority" in the family.
Senior figures from across the political spectrum, including Labour leader Sir Keir Starmer, have sent their condolences to Mr Johnson.
Sir Keir tweeted: "I'm very sorry to learn of the prime minister's loss. My condolences to him and his family."
Conservative party chairwoman, Amanda Milling, said she was "thinking of Boris Johnson and his family this evening", adding, "Our thoughts and prayers are with you."
Tory MP, Conor Burns, who is a friend of the prime minister, tweeted: "So sad to hear of the death of Boris Johnson's mum. Thoughts and prayers are with him and the whole of the Johnson clan."
Mrs Johnson Wahl, whose father was president of the European Commission for Human Rights in the 1970s, married Stanley Johnson in 1963 before completing her degree at Oxford University as the first married female undergraduate at her college.
The couple had four children - Boris, journalist Rachel, former minister Jo and environmentalist Leo. They divorced in 1979.
As an artist, Mrs Johnson Wahl made her name as a portrait painter, with actress Joanna Lumley and author Jilly Cooper among her subjects.
In 1988, she married American professor Nicholas Wahl and moved to New York - where she began painting cityscapes. She returned to London in 1996 following his death.
At the age of 40, she was diagnosed with Parkinson's disease but continued painting, steadying herself with a walking frame as she worked.