Jack Griffin loses out on his dream job and becomes a high school teacher of Advanced Placement biology in his hometown of Toledo, Ohio.
When Jack leaves his class unattended, a student injury sets off an official investigation and lands Jack in "teacher jail". An aggressive teacher's union rep sets her sights on Principal Durbin. The students' excitement for a substitute teacher are dashed when they find out it's Helen.
While Principal Durbin struggles with budget cuts, Jack discovers his students pity him - so he rallies, making a splash at the school bake sale and getting kicked out of the bookstore for life.
When Jack gets into a petty dispute with the student council president, the situation escalates much too far; Stef sells makeup at school as a side business.
Jack reluctantly agrees to go out on the town with Mary, Stef, and Michelle; his superiority complex proves difficult for the women to overcome; principal Durbin feels threatened when Helen fills in for him on the school's morning announcements.
When Jack is attracted to a student's mother at a parent-teacher conference, he feigns interest in her son; a group of parents complain to principal Durbin when they notice a piece of controversial student art from Mary's class.
Jack receives an offer from Miles' publisher to write a book of feel-good philosophy that could be his ticket out of Toledo. Durbin accidentally sets off an emotional firestorm when he reveals that while Stef chose Mary as her emergency contact, Mary chose Michelle.
Jack finds out his ex-girlfriend Meredith needs a venue for a charity fundraiser and has the perfect place: his student Victor's house. Victor and the other kids are inspired by Jack to party for the first time.
Jack is incensed when his dead mom's former lover shows up and suggests they commemorate her birthday. Jack taps his students to help him retaliate, but the students' hands are already full - of crying robot babies. Stef's kindness toward Dale the janitor sends the wrong signals.
When Jack casually gives Durbin some marriage advice, it backfires, gets Durbin kicked out of the house, and Jack takes him in. The A.P. Bio kids tell Jack if they can get Miles' DNA, they'll learn a little biology while pulling off the ultimate revenge.
When one of Jack's students anonymously reports him for canceling their much-anticipated fetal pig dissection, he sets out to find the snitch. Durbin's chances at Principal of the Year are in jeopardy when the superintendent visits.
Jack successfully convinces Miles that Devin is his illegitimate son; Durbin, Mary, Stef and Michelle clash on the Sadie Hawkins dance theme.
Jack takes interest in a revenge mission on behalf of the kids; Mary, Stef and Michelle believe they've discovered an otherworldly presence.