The original pilot episode aired on September 7, 2003, a full year before the series officially premiered on September 12, 2004, after Nickelodeon ordered it to series in early 2004.

The show was created and executive produced by Scott Fellows, who was also the head writer for The Fairly OddParents and later created Johnny Test.

The fictional setting, James K. Polk Middle School, is named after the 11th President of the United States and uses gold and green school colors with a wolf mascot.

During the first season, nearly all the action took place inside the school or on its grounds, but season 2 introduced more outdoor shots and scenes off school property, culminating in the finale, which took place almost entirely away from the school.

Jim J. Bullock played Mr. Monroe as a main cast member in season 1 before shifting to a recurring role in seasons 2 and 3, while Daran Norris's character Gordy went the opposite way, starting recurring in season 1 and becoming a main role for seasons 2 and 3.

The series debut on September 12, 2004, drew a 4.5 rating with 914,000 tween viewers, which Variety's Denise Martin described as "healthy, but not as stellar".

Reviewing the series finale, Robert Lloyd of the Los Angeles Times called the show "one of the best series on television — a show that took genre conventions and ran them through unpredictable changes".

In June 2008, lead actor Devon Werkheiser signed a development deal with Nickelodeon for a spin-off following his character into high school, but it was never greenlit because creator Scott Fellows was busy with Big Time Rush, Daniel Curtis Lee was committed to Zeke and Luther, and Lindsey Shaw was working on 10 Things I Hate About You.

In 2021, Werkheiser, Daniel Curtis Lee, Lindsey Shaw, and Scott Fellows pitched a reboot called Ned's Declassified Adulthood Survival Guide to Nickelodeon and AwesomenessTV, but the studios turned it down and refused to let them shop it elsewhere.

In February 2023, Devon Werkheiser launched a podcast titled Ned's Declassified Podcast Survival Guide together with former co-stars Lindsey Shaw and Daniel Curtis Lee.