It is particularly devastating for the couple as they have two young children together, Oscar, five, and three-year-old Felix. One crumb of comfort for the actress, who shot to international fame as Agent Scully in hit sci-fi shows The X-Files, is they split on good terms.
A representative for the 43-year-old actress told Us Weekly:
'Gillian Anderson and her partner Mark Griffiths have amicably separated after six years together.'
The news will come as a shock to fans of the cult show, whose votes helped her top the FHM World's 100 Sexiest Women poll in 1996.
It is not the first time the mother-of-three has suffered heartbreak.
She married X-Files assistant art director Clyde Klotz on New Years Day 1994 in a Buddhist ceremony on the 17th hole of a golf course in Hawaii.
They also had a daughter Piper Maru together in September that year.
However the union ended in an unhappy note, as they divorced in 1997.
The Last King of Scotland star was also married to documentary maker Julian Ozanne for two years before parting ways in 2006.
It comes just months after she admitted to having had lesbian flings in the past to gay magazine Out.
She said: 'I was in a relationship with a girl for a long time when I was in high school.'
But the Moby Dick favourite also said she was far too attracted to men for it to something more long-lasting.
Gillian said: 'If I had thought I was 100% gay, would it have been a different experience for me? 'Would it have been a bigger deal if shame had been attached to it and all those things that become huge life-altering issues for youngsters in that situation? 'It’s possible that my attitude around it came, on some level, from knowing that I still liked boys' The actress also admitted that while she is certainly more interested in men, she still likes to experiment with women from time to time.