Actress Diana Quick, 61—who saved him from alcoholism—moved out of their £1.7million London mansion and ended their 27-year relationship.
A source said: 'This is a devastating split. Everyone thought their relationship was rock solid, but Diana wants nothing more to do with him.'
Friends believe Bill's packed workload after his Bafta-winning performance as ageing rocker Billy Mack in the 2003 film, Love Actually, is behind his split from Diana.
One said: 'Bill's career has taken off over the last few years, turning him into a huge star.
'But it's been a different story for Diana as it's harder for older actresses to find work. The pair have lived increasingly separate lives, and she's been left on her own.'
Pals now fear the 58-year-old actor may struggle to cope without Diana, who first found fame in TV's Brideshead Revisited. He called her his 'wife', though they never married, and she was seen as a stabilising influence.
Bill is a renowned workaholic and has already battled a string of booze and drug demons, previously admitting: 'I don't have a moderate muscle in my body. I used to drink for England, Ireland, Scotland and Wales.'
Our source added: 'Diana has been Bill's rock for years. He was a mess but got himself clean and became one of our most successful actors. One of the reasons was the support he got from Diana. They are saying publicly it is a mutual split, but the truth is that Diana got fed up with Bill and ended it.'
The couple met in 1981 and have a 24-year-old actress daughter Mary together. Bill once described Diana as the 'love story of my life'.
But recently she has spent more time at their Suffolk cottage, and is now understood to have found a new home. The source added: 'They're living apart and have cut all contact. It's tremendously sad, but it's all over.'
Last night, the couple said in a statement: 'Bill and Diana separated amicably. They remain great friends.'