Diana Goodman, a suburban mother with bipolar disorder, waits for her teenage son to return home after he has broken curfew. Diana's daughter Natalie is also awake completing her homework. Her son returns home and Diana's husband Dan wakes up, and the family prepares for the day ahead until Diana, disoriented, prepares sandwiches on every surface in the kitchen, including the floor ("Just Another Day").
Natalie, a pianist who hopes to attend the Yale School of Music, laments the stress of being an overachiever while practicing for an upcoming recital in the school music room ("Everything Else"). She runs into her classmate Henry and they bond over their shared love of music. Diana regularly visits her psychiatrist Dr. Fine, who prescribes a series of medications to treat her bipolar disorder that all cause unpleasant side effects. Dan, waiting in the car, mourns the current state of his life and his and Diana's relationship. When Diana says her new medication makes her feel numb and emotionless, Dr. Fine declares her stable ("Who's Crazy?/My Psychopharmacologist and I").
Henry confesses his romantic feelings for Natalie and they start dating ("Perfect for You"). Diana mourns the full spectrum of emotions she once felt and flushes her medications at her son's urging ("I Miss the Mountains"). Henry joins the family for dinner ("It's Gonna Be Good"), but when Diana brings out a cake for her son's 18th birthday, Dan gently reminds her that he died as an infant and her visions of him are delusions ("He's Not Here"). Diana reveals to Dan that she stopped taking her medication and tells him he will never understand the pain she feels ("You Don't Know"). Dan begs her to help him understand, but Diana is torn between the comfort her delusion brings her and confronting the painful reality of his absence ("I Am the One"). Natalie vents to Henry about Diana's attachment to her firstborn child and their strained relationship ("Superboy and the Invisible Girl").
Diana visits a new psychiatrist, Dr. Madden, who agrees to start with talk therapy. Her son reappears and reasserts his control over Diana's life; her delusions disturb her, but she is also comforted by his presence ("I'm Alive"). Diana later tries hypnotherapy with Dr. Madden; she opens up about her son's death and her relationship with Natalie, admitting she had Natalie to be a replacement child and Diana was unable to hold her in the hospital. Meanwhile, Natalie messes up her piano recital after realizing her parents are not there ("Make Up Your Mind/Catch Me I'm Falling"). Dr. Madden encourages Diana to begin getting rid of her son's things, and she has another vision of him ("I Dreamed a Dance"). The vision tells Diana the only way they can be reunited is if she is dead, and she attempts suicide ("There's a World").
Diana survives the suicide attempt, and Dr. Madden tells Dan that due to the severity of Diana's condition, electroconvulsive therapy is among the last treatment options left. Dan reminisces about their relationship and how he has stood by her through everything ("I've Been"), while Diana is furious at the suggestion she undergo ECT ("Didn't I See This Movie?"), Dan convinces Diana that the treatment is a chance to get back to normal, and she reluctantly agrees ("A Light in the Dark").
Diana undergoes ECT, while Natalie experiments with drugs and frequently goes clubbing. The two have a shared hallucination ("Wish I Were Here"). When Diana is released from the hospital, she reveals that she has lost her memories from the past 19 years, including her son and daughter. Dan remains optimistic that her memories will return, while Natalie is upset her mother agreed to the treatment in the first place ("Song of Forgetting"). Henry, worried about Natalie's substance use and self-destruction, asks her to the upcoming school dance and she declines ("Hey #1").
Dr. Madden assures Dan that Diana's memory loss from ECT is normal. Dan is hesitant to remind her about their late son, given her mental illness first manifested after the trauma of his death ("Seconds and Years"). The family goes through old photo albums to jog Diana's memory, leaving out any mention of their firstborn ("Better Than Before"). Diana's vision of her son appears and reminds her there is an important part of her life she has forgotten ("Aftershocks"). Henry again asks Natalie to the dance and she again declines, though he says he will come pick her up that night in case she changes her mind ("Hey #2").
At a follow-up visit, Diana tells Dr. Madden she knows there is something important from her past she still can't remember. Dr. Madden, unaware that Dan has been keeping it from her, accidentally reveals the existence of her dead son ("You Don't Know (Reprise)"). Diana returns home and finds her son's music box, and Dan reluctantly reminds her of the circumstances of his death at 18 months old from an intestinal blockage, which all the doctors had missed ("How Could I Ever Forget?") but the confused Diana says she remembers him as a teenager due to having hallucinated him. The couple argue over Dan's insistence that she undergo more ECT and his refusal to tell her their son's name ("It's Gonna Be Good (Reprise)").
Diana asks Dan why he stays with her despite everything her illness has put him through. He reminds her of the vows he took when they married and promises he is committed to her no matter what. Henry, waiting to take Natalie to the dance, pledges the same to her ("Why Stay?/A Promise") and she agrees to go with him. The vision of Diana's son reappears ("I'm Alive (Reprise)") and threatens Diana, telling her the doctors lied to her.
Natalie takes Diana to visit Dr. Madden, telling Henry that she will meet him at the dance later. Diana expresses her frustrations to Dr. Madden that years of treatments haven't helped her and wonders if her grief over her son's death can even be treated ("The Break"). Dr. Madden unsuccessfully pleads with her to continue treatment ("Make Up Your Mind/Catch Me I'm Falling (Reprise)") but she leaves, deciding not to undergo more ECT. Diana and Natalie have a heart-to-heart, noting their similarities ("Maybe (Next to Normal)"). Diana drives Natalie to the dance, where she frets to Henry that she will struggle with her mental health the same way as her mother. Henry promises he will stand by her regardless of what happens in the future ("Hey #3/Perfect for You (Reprise)").
Diana returns home and tells Dan though she loves him, she is leaving, as they each need to grieve their son on their own ("So Anyway"). After she leaves, a devastated Dan finally acknowledges the vision of his late son, and they embrace. For the first and only time in the show, Dan and Diana's son is called by his name: Gabe ("I Am the One (Reprise)").
Natalie returns home from the dance to find her mother gone and her father sitting in the dark. She turns on a lamp, telling Dan, "We need some light." Natalie continues her relationship with Henry, while Diana temporarily moves in with her parents. Dr. Madden recommends another psychiatrist to Dan, so he can begin his own journey of grieving Gabe's death. The cast, including Gabe, acknowledge the difficulty of moving forward but hopeful that they will adjust to the changes in their lives ("Light").