In 1900, John W. Thackery, a brilliant yet tortured doctor working at the Knickerbocker Hospital in New York, ascends to the role of chief surgeon after the unexpected departure of his mentor, J.M. Christiansen. Though Thackery wants Everett Gallinger, his own protégé, to take over the assistant chief position, Cornelia Robertson, daughter of the hospital's major benefactor, insists he hire Algernon Edwards, a talented black doctor who trained in London and Paris. Edwards encounters enmity and resentment on his first day at the Knick, but his desire to remain prevails after joining Thackery, Gallinger, Dr. Bertram "Bertie" Chickering, Jr. and Nurse Lucy Elkins in the operating theater for a daring surgical procedure.

Thackery weighs performing surgery on a former flame, and orders Gallinger and Chickering to experiment on pigs. Barrow goes to extremes in order to pay off a debt and recover a missing tooth. After a bad day at work, Edwards takes out his frustrations at a local bar. Robertson is relieved when her pleas about treating a patient with typhoid fever are finally heard.