- Tom Hanks as Robert Langdon, a professor of symbology at Harvard University.
- Felicity Jones as Dr. Sienna Brooks, a doctor who helps Langdon escape.
- Omar Sy as Christoph Bruder, head of the SRS team.
- Ben Foster as Bertrand Zobrist, a transhumanist scientist, intent on solving the world's overpopulation problem.
- Irrfan Khan as Harry "The Provost" Sims, head of The Consortium, helping Zobrist in his mission.
- Sidse Babett Knudsen as Elizabeth Sinskey, head of the World Health Organization.
- Ana Ularu as Vayentha, The Consortium's agent in Florence who has orders to follow Langdon.
- Jon Donahue as Richard
Directed by Ron Howard