The film kicks off in a lively supermarket where an unnamed Mother (Amy Adams) is navigating the aisles with her curious two-year-old son. In a chance encounter, she bumps into an old friend, Sally, who inquires about her well-being. With an air of honesty, the Mother confesses that motherhood has drained away the essence of who she once was, leaving her feeling somewhat adrift in her new identity.
As she juggles caring for her son, her Husband (Scoot McNairy) remains often out of the picture due to work commitments, leaving the Mother with the weight of parental responsibilities. Her love for her son is undeniable; however, she increasingly loathes the societal expectations placed upon her. These include the unnecessary bonding rituals with other mothers at a club referred to as “Book Babies,” where she feels both out of place and embarrassed. This feeling peaks when her son unexpectedly chooses to exclaim a colorful word instead of his name in front of the other children.
As her day progresses, she encounters fellow moms—Miriam (Mary Holland), Jen (Zoe Chao), and Liz—who embrace her deadpan humor, finding amusement in her candidness despite her struggles. The Son draws her attention to an unsettling fuzzy spot on her back, leading the Mother to inspect the mirror, where she discovers a peculiar patch of white hair and a transformation of her teeth into sharp points. When she broaches these strange alterations with her Husband, he's dismissive, further exacerbating her frustration. The lack of shared domestic duties on his part only adds to her mounting stress.
As the Mother becomes increasingly aware of a notable bump on her back, she resorts to poking it, resulting in an alarming eruption of pus, followed by an unsettling revelation of a hair clump being extricated. In one particularly chaotic outing to the park, while attempting to bond creatively with her son through messy painting activities, she experiences a tumble that seems to trigger a cascade of bizarre occurrences.
That evening, an unsettling dream begins with her Son bringing her a dead rat, only to reveal a disturbing sight of dead animals scattered outside, allegedly dropped by local dogs with darker intentions. The dream transforms into a shocking wake-up, where she grapples with her Son who has a large, unpleasant surprise for her. In the shower, she makes an even stranger discovery—six additional nipples sprouting from her body.
Seeking answers, the Mother visits the library and consults with Norma (Jessica Harper), who hands her a book about transformations, particularly within maternal instincts comparable to those of dogs. This newfound knowledge sparks her transformation journey, leading her to claim the identity of “Nightbitch.” She mingles with a pack of likeminded women, who are suggested to be her fellow mothers from “Book Babies,” showing how far they've all transformed in their own right. This rekindles a sense of passion between her and her Husband, allowing the Mother to embrace a more instinctive way of living with her son, even eating more like an animal as she forsakes utensils at the table.
While attempting to reconnect with her art, she joins old colleagues at dinner, feeling overshadowed and marginalized by their conversations. A conversation with Naya (Ella Thomas) ignites discussions about motherhood, inspiring the Mother to chase her own artistic expression again. However, her struggles with mundane food lead her to abandon grace in favor of primal urges, as growling and bickering take center stage at the table.
The tension between the Mother and her Husband comes to a head as she confronts him about his lack of involvement in their son's life; this ultimately leads to an agreement of separation. Yet, the bond with their son weakens, making them reconsider their situation, especially after an unfortunate incident involving their family cat, illustrating the consequences of her transformations.
In an attempt to channel her newfound artistry, the Mother integrates her experiences with her pack of mothers as they collectively express their frustrations while building camaraderie. Hosting an art gallery show allows her to showcase her growth, surrounded by her fellow moms, as well as her former colleagues and even her Husband. This event becomes a turning point, leading to a reconciliation when both partners reveal long-hidden sentiments. They embark on a family picnic, rekindling the joy and connection they once shared.
As the narrative draws to a close, a pivotal moment occurs as the Mother delivers her second child, a daughter. The audience is left with a haunting howl echoing through the air, hinting at the profound changes that await. The film skilfully weaves together themes of transformation, identity, and the intricate bonds of motherhood, leaving viewers with much to ponder long after the credits roll.
