Following the huge success of X-Men: The Animated Series, Marvel's then-creative director Avi Arad and Toy Biz CEO decided to create more Marvel animated series to sell toys. Among these projects, Spider-Man: The Animated Series became the most successful. John Semper Jr., personally chosen by Stan Lee, took over the series, which had a rocky start after the original producer's departure. While dealing with mandatory characters that had already been produced as toys and the strangest censorship in television history, Semper successfully wove a long-running story that included flashbacks and character development. As a result, one of the best versions of Spider-Man was brought to the screen.

Semper managed to follow the vision of the story as the writer of nearly every episode. He balanced the melodrama of Peter Parker's (Christopher Daniel Barnes) double life with superhero action. The best episodes of the series often drew inspiration from the original comics. The episode "Guilty" begins with Peter mourning the loss of Mary Jane Watson (Saratoga Ballantine). As Peter considers retiring from his Spider-Man life, he learns that Daily Bugle's editor-in-chief Joseph "Robbie" Robertson (Rodney Saulsberry) has been arrested at a crime scene and is accused of being involved with a crime boss. Knowing Robbie is innocent, J. Jonah Jameson (Ed Asner) takes to the streets to conduct his own detective work and is even willing to set aside his rivalry with Spider-Man to ensure Robbie's release.

The episode "Duel of the Hunters" begins with Peter undergoing a horrific mutation into a Man-Spider during a battle between Spider-Man and the Punisher (John Beck). As the creature escapes into the city, Dr. Mariah Crawford (Susan Beaubian) learns about the mutation and calls her boyfriend Sergei Kravenoff (Gregg Berger) to follow Spider-Man while she seeks a cure. The episode also features Michael Morbius (Nick Jameson) and explores the differences between monsters and humans quite well. The design of the Man-Spider reflects an effective body horror and the tragedy of Peter's personality occasionally surfacing to influence the creature's actions.

The episode "Tombstone" demonstrates that the writers could create an episode where Spider-Man is not the main character. When Alisa Silvermane (Leigh Allyn Baker) learns that a story is going to be published about her father taking over a crime empire, she tasks her father's enforcer Tombstone (Dorian Harewood) with stopping it. Re-establishing a former friendship with Robbie Robertson, she blackmails him into suppressing the story due to past reasons. She also tries to further blackmail Robbie by forcing his son Randy (Alfonso Ribeiro) to join a crime gang.

The episode "The Black Cat" showcases Felicia Hardy's (Jennifer Hale) transformation from one of Peter's civilian friends into a playful, occasionally adversarial character beloved by comic fans. She has been transformed to test a super soldier formula obtained from her father John Hardesky (John Phillip Law), who was kidnapped by Kingpin (Roscoe Lee Browne) from S.H.I.E.L.D. Hale demonstrates her wide range in voice acting by smoothly transitioning from Felicia's normal speaking voice to a deeper, more confident tone when empowered. The rest of the episode is a solid mix of action and melodrama.