Depp, 53, has agreed to pay Heard $7m (£5.6m; €6.6m), which she says she will donate to two charities.
Heard, 30, will get to keep the couple's dogs, Pistol and Boo, who were at the centre of scandal when she took them to Australia illegally in 2015.
She had accused Depp of domestic abuse - a claim he denies.
According to court documents, she said Depp had been physically abusive to her, culminating in him throwing a mobile phone at her face during a fight in February last year.