In 1956, former nightclub singer and single mother Virginia Johnson becomes the assistant to renowned OBGYN William Masters. They embark on their pioneering study in human sexuality while trying to navigate their personal feelings for each other. Masters' wife Libby tries to conceive a child to save her marriage. Dr. Ethan Haas chafes under the supervision of Dr. Masters and deals with a changing society. University Provost Barton Scully struggles to support his protege William Masters while dealing with a long-held personal secret.