The film opens with Deanna Miles (Melissa McCarthy) along with her husband Dan (Matt Walsh) taking their daughter Maddie (Molly Gordon) to begin her senior year at Decatur University. Deanna is filled with anticipation for an upcoming trip to Italy, but this joy is abruptly shattered when Dan informs her that he wants a divorce, having fallen for someone else. Compounding her heartbreak, he reveals that he is selling their home, forcing Deanna out. Angrily, she kicks his car and hails an Uber to return home.
Arriving at her parents' house, Deanna finds solace with her mother, Sandy (Jacki Weaver), and father, Mike (Stephen Root). They reminisce about how Dan had previously made Deanna abandon her education due to an unexpected pregnancy, which left her without a degree. In a comedic moment, Mike nearly shoots their dog in a fit of rage directed at Dan.
Determined not to wallow in self-pity, Deanna plays tennis with her supportive best friend, Christine (Maya Rudolph). Here, she laments her situation until she has a revelation: she refuses to let Dan dictate her life any longer. Deanna surprises Maddie in her dorm with the news of her divorce and her ambitious decision to enroll at Decatur University for a year to attain a degree in archaeology. Maddie, stunned by her mother's transformation, is left momentarily speechless.
As Maddie introduces Deanna to her college friends—Amanda (Adria Arjona), the anxious Debbie (Jessie Ennis), and Helen (Gillian Jacobs), who has recently emerged from a long coma—Deanna feels a mixture of excitement and apprehension. She later meets her unusual roommate Leonor (Heidi Gardner) who adds an extra layer of quirkiness to her new college life.
In her archaeology class taught by Wayne (Chris Parnell), a former classmate, Deanna encounters Jennifer (Debby Ryan), the campus "mean girl." The mockery aimed at Deanna's mom attire and her reactions to Wayne's nerdy jokes adds to her feeling of incompatibility in this vibrant collegiate world.
The plot thickens when Deanna heads to sign the divorce papers with Christine only to bump into Dan accompanied by his new fiancée, Marcie (Julie Bowen). The encounter turns into a verbal duel mediated with sarcasm and rife insults. Seeking to bond with her daughter, Maddie invites Deanna to a get-together with her friends. After facing another barrage of jests from Jennifer, Deanna undergoes a fabulous makeover at Maddie’s insistence, leading her to meet Maddie’s boyfriend, Tyler (Jimmy O. Yang), and his friend Jack (Luke Benward).
A wild night of partying culminates in both Deanna and Maddie experiencing the infamous "walk of shame" after spending a night at the fraternity, leading Maddie to shockingly discover that her mother spent the night with Jack. As things progress, Jack develops feelings for Deanna, leading to a whirlwind romance that brings them back into the library stacks, solidifying their bond.
Deanna becomes a confidante to Debbie and the other girls, inspiring them to embrace their individuality and strengths, which further cements her newfound role as a mentor. The girls attend an 80's themed party where Deanna’s unexpected victory in a dance-off against Jennifer earns her the admiration of her peers.
However, tension arises when Deanna must give a presentation for class. Anxiety overtakes her, causing her to faint in front of her classmates. In a comedic twist, she later encounters Dan and Marcie at a restaurant, where they gloat about their upcoming trip to Italy. Yet, Deanna gains the upper hand by revealing that Jack, her recent fling, is actually Marcie's son.
On the day of Dan and Marcie's wedding, Deanna, along with her friends, indulges in weed-laced chocolate, which leads to chaotic antics as they crash the reception, fueled by a mix of anger and sadness about her past with Dan. Despite the unfolding disaster, they garner unexpected support from Helen's social media following, ultimately turning the party into a success with a surprise appearance from Christina Aguilera (Christina Aguilera), who joins in to elevate the celebratory chaos.
As the semester progresses, Deanna faces yet another challenge during a presentation but conquers her nerves when her supportive friends rally around her. The year culminates with a shared graduation between Deanna and Maddie, surrounded by loving friends and family. In a humorous turn of fate, Deanna tosses her cap into the air, inadvertently striking Dan, who proves to be a prime target for her newfound sense of freedom.
