Depp`s comedy Mortdecai flopped in cinemas, only making back $47.4m (£32m) of its $60m (£40.5m) production budget.
The actor`s 2014 sci-fi thriller Transcendence, meanwhile, only just made back its costs.
Denzel Washington is ranked second on the list, returning $6.50 (£4.39) on every dollar.
Will Ferrell, who topped the list in 2009 and 2010, is third this time after only bringing in $6.80 (£4.59) for every $1 spent on him on Anchorman 2: The Legend Continues and The Campaign.
That was just ahead of Liam Neeson, whose fourth place is down to the success of Taken 3 cancelling out Run All Night.
According to Forbes, the latter thriller cost $50m (£33.7m) and made $71.6m (£48.3m) back.
Adam Sandler, named the most overpaid actor in each of the past two years, was considered ineligible this year after signing a four-film deal with streaming service Netflix.
Chris Evans was Forbes` best value actor of 2015, the Captain America actor`s films returning an average $181.80 (£123) for every $1 he was paid.
How do the rankings work?
Each of an actor`s three major films up to June 2015 are counted in the list.
The only films which are not used for the basis of the survey are animated releases, ones where the actor only appeared in a minor role, or those which were released on fewer than 2,000 screens.
Forbes then take the estimated production budget away from the global box office returns for each film to work out each one`s operating income.
That figure is then added to the estimated total fee for each star across their three films to discover the final figure for return on investment.
Four actresses fill the next four places in the best value list.
Mila Kunis comes second with an $87.30 (£59) return on every dollar, while Scarlett Johansson, whose last three major films grossed a combined $2.58 bn (£1.742 bn), is third.
Gwyneth Paltrow, whose appearance in Iron Man 3 more than made up for her contribution to Mortdecai, is ranked fourth.
Last year`s winner, Emma Stone, comes fifth, with the disappointing performance of Aloha balanced out by 2014`s The Amazing Spider-Man 2.
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