Heard filed for divorce from the 52-year-old "Pirates of the Caribbean" actor on Monday in Los Angeles Superior Court, reported E! online.
The 30-year-old actress has cited the usual irreconcilable differences as the reason of their split.
Heard says in her divorce papers that they were separated on Sunday, May 22. She is asking for spousal support from Depp.
Sources says the pair had no prenuptial agreement in place.
The divorce filing comes shortly after Depp's mother, Betty Sue Palmer, reportedly passed away on Friday (May 20).
Representative for the former couple hasn't commented on the report yet.
Depp and Heard have recently been embroiled in a legal case in Australia after the actress brought two dogs into the country illegally.
She pleaded guilty in April to a charge of falsifying documents.
