The Pirates of the Caribbean star, 49, first began dating 39-year-old Paradis in 1998.
Depp had previously denied celebrity rumours they were about to split but his publicist confirmed in a statement the pair "have amicably separated."
Depp ended his previous relationship with Kate Moss to begin a long-term affair with Paradis; they went on to have two children, Lily-Rose, 13, and nine-year-old Jack, reports Newsbeat
Tabloid reports had stirred rumours of an imminent split when it had been observed the couple were leading increasingly separate lives, GMA News
reported in March.
Depp also dated actress Winona Ryder in 1990 and first came to fame when he appeared in Fox Television's 21 Jump Street
Depp and Paradis have homes in France, Los Angeles and even a private island in the Caribbean.
Paradis shot to fame in 1987 with a world wide hit, Joe le Taxi
. The French language hit made her a child star at the age of 14 and she has been the voice of cosmetic giant Chanel since 1991.