Barry B. Benson (Jerry Seinfeld) is "just an ordinary bee" in a hive located in Sheep's Meadow in Central Park in New York City. Barry recently graduated from college and is about to enter the hive's Honex Industries (a division of Honesco Corporation and owned by the Hexagon Group) honey-making workforce. Along with his best friend Adam Flayman (Matthew Broderick), Barry is initially very excited, but his latent, non-conformist attitude emerges upon finding out that his choice of job will never change once picked. This prompts Barry to leave the hive and see the world on a daily run with the macho, elite "Pollen Jocks", though Adam tries to talk Barry out of it. He thoroughly enjoys his new freedom, and is impressed by the process of nectar collection and pollination, but after being stuck to a tennis ball during a game and flying through a panicky family's car he decides humans are crazy and that he should go home. Unfortunately, it begins to rain and he crash lands on a windowsill. The apartment's occupants have just come home and they close the window before Barry can escape. After freaking out the people inside and nearly being squashed, he is rescued by a female florist human named Vanessa Bloome (Renée Zellweger) and gently put back outside. This unexpected act of kindness intrigues Barry, who goes back in to thank the woman even though doing so would violate Bee Law #1, "Don't talk to humans". Despite both of their expectations they develop an instant bond, bordering on attraction, and start hanging out together frequently. Of course all of their friends and family are completely upset by this relationship.
While they are going through a grocery store, Barry is shocked to discover that the humans have been stealing and eating the bees' honey for centuries, and decides to journey to Honey Farms, which supplies the grocery store with its honey. On the Honey Farms truck, he meets a mosquito named Mooseblood (Chris Rock). A windshield wiper flings the two in a tube and Barry tells Mooseblood about Honey Farms while Mooseblood tells him about how humans have always swatted mosquitoes. Mooseblood departs when he sees a Blood Mobile pass by, while Barry goes on to witness the artificial process by which the honey is gathered. He ultimately realizes that his true calling in life is to set the world right by suing the human race for stealing their precious honey. This is later shown on Hive at Five's especially on Bee Larry King starring a bee version of Larry King (voiced by Larry King). The trial initially goes well, until the main defense lawyer (John Goodman) goads Adam into stinging him by accusing Barry of several things which are insulting to the bees (having a pet-like relationship with Vanessa, being an illegitimate son, since all bees are sons of the queen bee and having incestuous flirtings with the female bees, since all bees are siblings) in order to show the less lovable side of bees, but Barry counters by producing the smoke-machine used by Honey Farms to drug and subdue their bees.
Barry wins the lawsuit, and all honey in the world is confiscated and returned to the bees. However, the defense lawyer warns them they are disrupting nature's balance meaning that the bees quit their jobs, which Adam comments to Vanessa that it might be true since bees had been living their previous lives over 27 million years. Too late, Barry and Vanessa realize that they were right: the sudden, massive stockpile of honey has put every bee out of a job, including the vitally important Pollen Jocks. Without bees pollinating the flowers, all plant life begins dying with the entire food chain close behind. To set things right, he and Vanessa find a way to save all the flowers by going to the Tournament of Roses Parade in Pasadena, California and bringing back with them all the pollen-filled flowers to re-pollinate the world. Barry and Vanessa fly the flowers as luggage on a flight from Los Angeles International Airport to John F. Kennedy International Airport. The flight begins to take a detour due to lightning, which would be fatal to the flowers, and in trying to intervene Barry accidentally knocks out the terrified pilots. Vanessa joins him and tries unsuccessfully to fly the plane, but in the meantime millions of bees have rallied together and arrive at the last minute to help them safely land.
Armed with the pollen of the last flowers, Barry and the Pollen Jocks manage to reverse the damage and save the world's flowers, also restarting the bees' beloved honey production. Nothing is mentioned about the fate of companies like Honey Farms, though humans and bees are seen treating each other visibly better, and honey is supposed to be 'Bee approved'. Barry becomes a member of the Pollen Jocks while Adam is working as a krelman, helping to pollinate the plants while also running a law firm inside Vanessa's flower shop, as well as helping Vanessa, switching the name from "Vanessa's Flowers" to "Vanessa and Barry: Flowers; Honey; Legal Advice". As the film closes, his office door reads "Insects at Law." Mooseblood also works in his office with him as a lawyer(stating that he is already a bloodsucking parasite and only needed a briefcase), which is shown when Barry is interviewing a cow about the human exploitation of her milk.