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The fee is a guaranteed minimum earning for the film, On Stranger Tides, in which he reprises the role of Captain Jack Sparrow, but could increase if it is a box-office hit.
It places Depp at the top of the high-earning actors, above the likes of Tom Cruise, Tom Hanks and Mel Gibson, who each command around £18 million.
Studio bosses at Disney have agreed to the record pay deal because Depps high-profile Pirates co-stars, Keira Knightley and Orlando Bloom, are not returning for the next adventure.
Geoffrey Rush will again play Captain Barbossa while Penelope Cruz has been lined up for the female lead, although this has not been confirmed.
A source said: "The movie will feature flashbacks to Jack's early life."
Depp got £15 million for the third film, Dead Man's Chest, and stands to collect some £50 million from the whole series.
With the deal Depp joins the ranks of some of Hollywoods best known and highest-paid actors.
Here is a list of the Top 10 biggest payouts:
Harrison Ford (£38m) Indiana Jones 4
Tom Hanks (£29m) Angels and Demons
Cameron Diaz (£28.5m) What Happens in Vegas
Jim Carrey (£23m) Cable Guy
Will Smith (£18m) Hancock
Sacha Baron Cohen (£16m) Borat
Mel Gibson (£17m) Lethal Weapon 4
Matt Damon (£15m) The Bourne Supremacy
Tom Cruise (£12m) Mission: Impossible III
Robert Pattinson (£10m) Twilight Saga