Cleo (Rowan Blanchard) is a teenage girl living in the shadow of her older sister, Molly (Paris Berelc), whose popularity gets her recognized by everyone at school. Although Cleo is hardly noticed compared to her sister, she is an excellent student, but is introverted and somewhat sarcastic and cynical.
Cleo’s science teacher, Mr. Perkins (Alex Désert), sees her potential in science and decides she needs a challenge for her class project; she is to determine a mystery substance and transform it into its crystal state. As she works on the experiment at home, while Molly hosts a dinner for her lacrosse team, a moth flies by and distracts Cleo, causing her to accidentally spill unknown chemicals into her solution. The steam produced ends up turning the moth invisible, leading Cleo to chase it around the house, full of guests, before it gets away.
Later, while Molly is preparing for bed, the moth returns, attracted to the light from the bathroom. The moth falls into a cup of water containing an antacid Molly is about to drink, and she unknowingly consumes the moth which renders her invisible.
The next morning, Molly is horrified when she cannot see herself and discovers why from Cleo. She must attend school to participate in the season opener for her lacrosse team, which college scouts will be watching. As it is Halloween, she decides to wear her costume to mask her invisibility, but when the costume also turns invisible, Molly has Cleo wear the costume and pretend to be her at school. Cleo attends the pep circle for the lacrosse team while Molly grabs a microscope from the science classroom so Cleo can figure out how to make her visible again. In the process, Molly hears Carter (Will Meyers), a boy Cleo likes, talking with George (Karan Brar) about Cleo; she manages to secure a date for her sister by pretending to be her and asking Carter out. Things get complicated when George finds out Molly’s invisibility, and her boyfriend Coug (Austin Freyberger) questions why she is constantly avoiding him. Later in the lacrosse game, Cleo has a rough start but slowly gets into the game with Molly’s help, resulting in a victory for the team.