The series takes place in modern-day Paris and revolves around the adventures of two teenagers, Marinette Dupain-Cheng and Adrien Agreste. When evil arises, they transform into their superhero personas, Ladybug and Cat Noir respectively, using magical jewels known as Miraculouses, which are powered by small animal-themed cosmic beings called Kwamis (theirs being named Tikki and Plagg respectively). All the while, Marinette and Adrien struggle with their feelings for each other, not knowing each other's secret identities – Marinette is in love with Adrien, but not Cat Noir, while Adrien is in love with Ladybug, but not Marinette.
Their main enemy is Gabriel Agreste, Adrien's father. As the supervillain Hawk Moth, he attempts to claim Ladybug and Cat Noir's Miraculous jewels. Using the Butterfly Miraculous, he creates akumas, butterflies infused with negative energy, to "akumatize" Paris' everyday citizens, turning them into supervillains when they experience negative emotions. He intends to use the jewels to wish his wife, Emilie, back to life after she had fallen into a coma from using the damaged Peacock Miraculous before the events of the series. He is sometimes aided by his assistant Nathalie Sancoeur, who, using Emilie's jewel as the supervillain Mayura, uses feathers called amoks to create sentimonsters, magical lifeforms with a seemingly endless variety of forms and abilities.
As Hawk Moth's villains become tougher, Master Wang Fu, the Guardian of the Miraculous, allows Ladybug to borrow different Miraculouses and recruit her other classmates and friends as superheroes. Marinette and Adrien also encounter guitarist Luka Couffaine and fencer Kagami Tsurugi respectively, developing feelings for them, which further complicates their romance. They also become enemies of Lila Rossi, a pathological liar with multiple identities; Chloé Bourgeois, a Ladybug fan and former superhero who turned against her; and Félix Fathom, a sentimonster in the form of Adrien's maternal cousin, who wants to claim the Peacock Miraculous in order to take control of his own life.
Hawk Moth eventually exposes Master Fu, forcing him to make Marinette the Guardian; she starts training under Su-Han, the leader of the Guardians. Nathalie falls ill from using the Peacock Miraculous, so Hawk Moth repairs it and fuses it with his Miraculous to become Shadow Moth, able to create both villains and sentimonsters. Marinette's best friend, Alya Césaire, learns her secret identity, and Luka discovers Ladybug and Cat Noir's identities by accident. Over time, Marinette starts to prioritize Alya and other temporary heroes over Cat Noir, causing a severe strain on their relationship.
Félix eventually recovers the Peacock Miraculous, and in exchange, Gabriel gains access to most of the other Miraculous jewels, renaming himself "Monarch". Ladybug and Cat Noir once again become the only two heroes.
Monarch attempts to capture the heroes himself, but he is accidentally left with a scar that slowly spreads through his body. Realizing his days are numbered, he collaborates with Tomoe, Kagami's mother, and turns the Miraculouses into special rings, enabling him to give his supervillains Miraculous powers. Marinette temporarily falls in love with Cat Noir while Adrien abandons his crush for Ladybug to be with Marinette, but eventually they enter a true romantic relationship; however, Gabriel and Tomoe insist their children should be together. Meanwhile, Chloé and Lila plot against the heroes, the latter seeking to overthrow Gabriel. Félix, on the other hand, falls in love with Kagami and the two learn Ladybug's identity; the former later joins the heroes' side. Gabriel ultimately seizes the Miraculouses and makes a wish to revive Emilie in exchange for his own life, with Lila getting the Butterfly Miraculous.