For years, high school students have been confined to their customary roles such as jocks, princesses, nerds, and outcasts. However, as Bianca Piper (Mae Whitman) explains, today's students are breaking free from these stereotypical labels. Now, you'll find jocks engrossed in video games, princesses managing their mental health with medication, and nerds taking the reins of social dynamics. Amidst this, the not-so-attractive, slightly chubby Bianca walks through the crowded halls alongside her two stunning best friends: Jessica 'Jess' Harris (Skyler Samuels), an aspiring fashion designer, and Casey Cordero (Bianca A. Santos), who is known for her fierce hacking skills. Despite their striking appearances, Bianca often feels invisible as she's overshadowed by the attention given to Jess and Casey.
When the school's notorious mean girl, Madison Morgan (Bella Thorne), extends a party invitation exclusively to Jess and Casey while snubbing Bianca, the latter reluctantly tags along after her friends convince her to go. It's at this party that she bumps into Wesley Rush (Robbie Amell), her neighbor and a former friend who is currently the charismatic captain of the football team and Madison's on-and-off beau. While Bianca harbors feelings for a guy named Toby Tucker (Nick Eversman), she struggles to muster the courage to approach him.
Encouraged by her newspaper supervisor, Mr. Arthur (Ken Jeong), Bianca agrees to write an article about social dynamics in the context of the impending homecoming dance. At home, her mother, Dottie (Allison Janney), a successful author who found inspiration in The Simpsons, pushes her daughter to explore her social life further.
At the party, a conversation with Wes reveals to Bianca that she is seen as the "Designated Ugly Fat Friend" (DUFF). Hurt and upset by this label, she lashes out by dousing Wes with her drink and retreats home, plagued by insecurities about her position within her social circle. The realization that people engage with her primarily to get closer to Jess and Casey ignites a desire to change her image. Although Wes offers some support by proposing they help each other out—she tutors him in chemistry while he helps her boost her confidence—things spiral into a series of comical shopping trips and awkward encounters.
Despite a budding friendship, things take a turn when a video of Bianca's mall antics goes viral, further isolating her from her peers and worsening her confidence issues. Wes attempts to make amends and encourages her to confess her feelings to Toby, which leads to another set of disappointments as Bianca realizes Toby only wanted to befriend her for her connections with Jess and Casey.
Bianca's emotional journey continues as she navigates the tumultuous waters of teenage friendships, identity, and romance. Eventually, during a key moment at the homecoming dance, Bianca steps into the spotlight, revealing her true self and indirectly challenging the toxic hierarchy of social labels. She confidently tells Madison that everyone experiences being a DUFF in some way, thus affirming her newfound self-acceptance.
As the story unfolds, Bianca transforms, leading to her crafting an impactful article on the essence of being a DUFF, which resonates with her peers and ultimately strengthens her bond with Wes. The film wraps up as Bianca embraces her individuality and confidence, discovering that she is more than just a label.
