Plot details are being kept under wraps and it is unknown who Mikkelsen will be portraying in the action-adventure sequel.
Phoebe Waller-Bridge also stars in the film, from filmmaker James Mangold.
Mangold is taking over directing duties after Steven Spielberg directed the previous four Indiana Jones installments. Spielberg, Kathleen Kennedy, Frank Marshall and Simon Emanuel are producing. John Williams is returning to score the project.
Lucasfilm is hoping to start production this summer with Mangold meeting with other talent.
Indiana Jones 5 is set to hit theaters on July 29, 2022. The last entry, Indiana Jones and the Kingdom of the Crystal Skull, was released in 2008.
A new Indiana Jones video game is also in development from publisher Bethesda Softworks and Lucasfilm Games. The title will feature an original story.
Mikkelsen is best known for starring in James Bond film Casino Royale, Rogue One: A Star Wars Story and Doctor Strange. He will appear in the third Fantastic Beasts film, replacing Johnny Depp as Grindelwald.