| Clive Owen | Dr. John W. Thackery |
| André Holland | Dr. Algernon Edwards |
| Jeremy Bobb | Herman Barrow |
| Juliet Rylance | Cornelia Robertson |
| Eve Hewson | Nurse Lucy Elkins |
| Michael Angarano | Dr. Bertie Chickering Jr. |
| Chris Sullivan | Tom Cleary |
| Cara Seymour | Sister Harriet |
| Eric Johnson | Dr. Everett Gallinger |
| Grainger Hines | Captain August Robertson |
| Zaraah Abrahams | Opal Edwards |
| Charles Aitken | Henry Robertson |
| Tom Lipinski | Phillip Showalter |
| Michael Nathanson | Dr. Levi Zinberg |
| Linda Emond | Anne Chickering |
| Jennifer Ferrin | Abigail Alford |
| Gibson Frazier | Harold Prettyman |
| Arielle Goldman | Genevieve Everidge |
| Emily Kinney | Nurse Daisy Ryan |
| Ntare Guma Mbaho Mwine | D.W. Garrison Carr |
| Molly Price | Effie Barrow |
| Anthony Rapp | Dr. Thurman Drexler |
| Reg Rogers | Dr. Bertram Chickering, Sr. |
| Perry Yung | Ping Wu |
| Lily Brahms | Clara Chickering |
| Phil Burke | Doctor |
| Dara Coleman | Ambulance Driver |
| Lizzy DeClement | Young Girl at Home for Fallen Women |
| Colman Domingo | Dr. Russell Daniels |
| Ylfa Edelstein | Nurse Baker |
| John Treacy Egan | Detective Satterlee |
| Brian Faherty | Fire Chief Croker |
| Caitlin Kinnunen | Suzy |
| Thomas Kopache | Samuel Reid |
| Ying Ying Li | Lin-Lin |
| Wade McCollum | Sidney Carton |
| Aedin Moloney | Sister Mary Michael |
| John O'Creagh | Tammany Hall Official |
| Lucas Papaelias | Eldon Pouncey |
| Dorian Scarfi | Moisha |
| Zuzanna Szadkowski | Nurse Pell |
| Dwayne A. Thomas | Bartender |
| David L. Townsend | Mr. Stern |
| Chandler Williams | Nelson Epps |
| Samuel Dunning | Injured Construction Worker |
| Jonathan Ercolino | Circus Goer |
| Robert John Gallagher | Irish Construction Worker |
| Alina Gerasimova | Nurse |
| Sean Harris | Footman |
| And Palladino | Gallery Doctor |
| Scott Radock | Bloody Burned Patient |
| Robert Sage | Surgeon |
| Christopher Weigel | Penn Medical Doctor |
| John Wilburn | Orderly |