In the series premiere of this medical drama set in a 1900s New York City hospital, accomplished Dr. John W. Thackery is named chief surgeon and is pressured by a major benefactor to hire a black doctor as his top assistant.

Already fuming over the hospital's faulty new electrical system, Thackery tasks Herman Barrow, the Knick's crooked superintendent, to deliver more cadavers so that he and his team can test out novel surgical procedures. With more patients dying, Edwards offers to share a procedure he learned in France, but is rebuffed by Thackery and Gallinger. Robertson addresses a typhoid-fever outbreak, Elkins is taken into Thackery's confidence and Sister Harriet breaks a taboo. Edwards finds an alternative way to perform his duties.

During surgery, Thackery's hand is forced by Algernon, which irks Gallinger. A recovering Abigail regrets her involvement with Thackery and Sister Harriet and Cleary make a couple of deals. Meanwhile, Bertie receives a scolding from his physician father who is unhappy with his son's career path and Lucy becomes privy to Thackery's secrets.

Barrow can alleviate a debt if he treats one of Collier's wounded men and also urges Capt. Robertson to buy one of Thomas Edison's new inventions. Meanwhile, Algernon tries a new approach to hernia surgery, the health of Everett and Eleanor's baby worsens, and Sister Harriet and Cleary head to Chinatown.

Refusing to collaborate with Dr. Zinberg on blood-transfusion research, an increasingly paranoid Thackery pushes himself to the limit, and beyond, in an effort to “solve the riddle” and beat his rival. Cornelia and Edwards arrive at a crossroads; Barrow trades one creditor for another; Lucy requests Bertie’s help. With the Knick in the midst of yet another crisis, Robertson calls for a vote.