Dramatic depiction of the lives of sex researchers William Masters and Virginia Johnson. In the opener, Masters begins conducting a secret study of human sexuality and meets Virginia Johnson, a former nightclub singer who joins the hospital secretarial staff and proves herself to be an asset to Masters' work.
Masters blames Johnson when the sexual response study is forced out of the hospital. To continue his research, Masters moves the study to a brothel but soon realizes that to manage the chaos of the cathouse he needs Johnson's help.
Research continues in the brothel but skewed data convinces Masters to get the study back into the hospital. Meanwhile, Johnson meets a new female doctor; Libby struggles to conceive; and Dr. Haas gets the case of a lifetime: a woman pregnant with quadruplets.
New participants are recruited on campus for the study and Johnson is shocked when her ex-husband wants to sign up. Meanwhile, Masters' mother visits but her new take on life stirs up painful memories; and Libby's attempt at playing matchmaker for Virginia and Ethan doesn't go as smoothly as she had hoped.
The study is expanded to include couples. Meanwhile, Johnson tries to connect with her son who prefers to spend time with his dad; Masters becomes anxious about becoming a father; and Ethan learns that dating the provost's daughter could impact his medical career.
Libby and Masters travel to Miami for rest, but he is drawn back into his work by a sexually adventurous couple next door. Meanwhile, Virginia tries to debunk Freud's theory that one kind of female orgasm is better than another; and Langham finds an unlikely cure for his sexual dysfunction in Margaret Scully.
Masters and Johnson become participants in their sexual response study, but Johnson fears their work is interfering with Masters' home life. Meanwhile, Libby pressures Dr. Haas to resume her fertility treatments in secret; Haas struggles to let go of his feelings for Virginia as his relationship with Vivian deepens; and Margaret Scully confronts her husband about their troubled marriage.
Masters and Johnson decide the best way to record their findings is to film them, but to do so they have to enlist outside help. Meanwhile, Johnson redoubles her efforts to get a college degree; Scully takes drastic steps to control his sexual impulses; and Haas and Langham convince each other of the merits of being a married man.
Masters and Johnson decide to film external reactions in the study, and must convince Lester and Jane that their footage won't cross the line into pornography. Meanwhile, Haas reveals he is Jewish; Libby keeps her pregnancy a secret from Masters; and Estabrooks observes Masters and Johnson's intimate relationship.
Conflicts escalate at the hospital during a nationwide civil defense drill; a former study participant reveals that she is pregnant and wants to know the identity of the father; Masters and Johnson disagree over whether to maintain study confidentiality; Haas learns he has been denied a job at the hospital; Margaret Scully seeks answers about her husband's sexuality from an unlikely source.
Masters and Libby compile study information for a hospital-wide presentation; DePaul and Johnson travel to a medical convention and DePaul opens up on why her work on the Pap smear is important; Virginia's ex-husband returns and finds Ethan playing father to his children.
Season 1 ends with Masters making a hospital-wide presentation of his work and being disappointed with the response. Meanwhile, Haas entertains a job offer at UCLA Hospital and considers what a move would mean for his relationship with Virginia; and Scully pursues electroshock treatment with the hope of curing his homosexuality, but Margaret has second thoughts about the risks involved.