Reality TV star Dina confirmed the news on Thursday, telling Us Weekly magazine she and her husband remain close but they have been living apart for some time.
When contacted about the reports, filmmaker Eastwood's representative said, "I know nothing about that."
The split news comes just four months after Dina reportedly checked into a rehabilitation clinic to tackle personal issues.
She and Clint married in 1996 and have one daughter together, 16-year-old Morgan, who appeared with her mother and half-sister Francesca in reality TV show, Mrs. Eastwood & Company, which aired last year.
This is Eastwood's second union - he was married to first wife Maggie Johnson for almost 30 years before they divorced in 1984.