The list, based on the last three films in which those included starred before June, revealed Depp returned only $1.20 (81p) for every $1 (67p) he was paid.
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.