NBC announced in May 2018 that they renewed the show for a second season.

Colin wears TeeTurtle shirts in every episode. The actor says, "I actually wore them to the fitting and they made it into the show since it's actually what I wear. Legit my whole wardrobe."

Show creator (and SNL alumnus) Michael Patrick O'Brien attended high school in the real Ohio town in which A.P. Bio is set: St. John's Jesuit High School in Toledo, Ohio.

The pilot was filmed in the 300 building at Millikan High School in Long Beach, California. Millikan High is also the Rams and has a blue and gold color scheme, just like the school in the show.

Wesley's bar is a place where teachers can sometimes be found to hang out after work starting in season 2. Wesley's bar is a real bar in Toledo, Ohio located at 1201 Adams St. The exterior shots used in the show are footage of the actual bar exterior.

The series premiered on February 1, 2018 for a special preview and made its official debut on March 1, 2018. NBC released the first three episodes on NBCUniversal streaming platforms after the February 1 broadcast premiere for early viewing.

After a pilot order in late January 2017, the project was ordered to series on May 8, 2017.

Tom Bennett plays Miles in the style of the Ricky Gervais character David Brent (The Office UK 2001). Coincidentally Tom Bennett appears with Ricky Gervais in "David Brent: Life on the Road 2016".

In May 2019, A.P. Bio Creator-Executive Producer Mike O'Brien broke the news that the sophomore sitcom had been canceled.

The show was canceled after 2 seasons due to a decline in viewers.

"Spinach quiche" are the last two words spoken in the entire series.