The series was originally going to be titled Jump Street Chapel, after the deconsecrated church building serving as the unit's headquarters, but Fox requested the change so viewers wouldn't mistake it for a religious program.

Jeff Yagher was originally cast as Officer Tom Hanson in the pilot, but after the pilot was filmed he was replaced and his scenes reshot with Johnny Depp.

Midway through the first season, Frederic Forrest was replaced by Steven Williams; on screen, Forrest's character Richard Jenko was killed off by a drunk driver to explain the change.

As the original cast grew too old to convincingly pass as high schoolers, younger actors like David Barry Gray were brought in as 'youthful' replacements to maintain the show's premise.

Johnny Depp was paid $45,000 per episode under his contract, found his resulting teen-idol status irritating, and was eventually released from his contract after the fourth season.

Set in the fictional city of Metropolis in the fictional Evergreen State, the series was primarily filmed in Vancouver, British Columbia, making it one of the first major TV series to use the city and helping establish it as a filming hub.

21 Jump Street was the first hit series for the fledgling Fox network, debuting in spring 1987 alongside Married... with Children and The Tracey Ullman Show, and in August became the first Fox series to win its timeslot against a Big Three network show.

The departure of Depp's and Dustin Nguyen's characters was never explained within the TV series itself, but the 2012 film adaptation retroactively explains that Officer Hanson was transferred to the DEA and later joined by Officer Penhall.