The four times Oscar-winning actor, 83, is said to remain close to his wife, but the two have been living apart for quite some time – they have not been pictured publicly together since 2011 and, according to a source, the two actually split in June 2012.
"Clint fell out of love with Dina a long time ago," a source told Us Weekly, noting that the separation was "amicable."
Clint, who has four times won an Oscar, married Dina in 1996 and the couple have one daughter together, 16-year-old Morgan.
His 48-year-old wife checked into rehab for help with depression and anxiety earlier this year, believed to have been caused by the stress of the breakdown of their marriage.
According to TMZ, the former news anchor entered an exclusive facility in Arizona.
In 2012, Dina stepped into the spotlight when she invited cameras into the family home for her own reality show, Mrs Eastwood & Company, which also starred the couple's daughter Morgan and Francesca, 19, Clint's daughter from a previous relationship.
The show – which ran for one season in 2012 – followed the lives of the Eastwoods in Carmel-by-the-Sea, California, where Clint was mayor from 1986 to 1988.
The twice-married Million Dollar Baby actor first wed Maggie Johnson in 1953. The couple had a daughter, Alison, and a son, Kyle together. Clint has five more children from other relationships, as well as his young daughter Morgan.
The news of the Hollywood star’s separation from his wife comes just days after the revelation that Michael Douglas and Catherine Zeta-Jones are "taking a break" after 13 years of marriage.
The stress of both of their struggles with health "has taken a toll on their marriage," a friend of the stars said on Wednesday.
A spokesman for Catherine said: "Catherine and Michael are taking some time apart to evaluate and work on their marriage."