The series was originally published from March 1972 through February 1985, and featured Spider-Man as the lead "team-up" character in all but ten of its 150 issues, and in six of its seven Annuals.

The third Marvel Team-Up series, written by Robert Kirkman, began publication in January 2005 and frequently featured Spider-Man.

Comics journalist Jonathan Miller summarized Marvel Team-Up in a retrospective article: The series was admittedly formulaic; either Spider-Man or that issue's guest-star would encounter a menace and then by sheer chance cross paths with another hero who would lend a hand.

The title's guest-stars were an equal mix of A-list characters whose presence was likely to increase sales and fledgling heroes being given exposure in the hopes of launching them into stardom but who for the most part continued to languish in obscurity.

[1]The series debuted with a March 1972 cover-dated issue[2] featuring Spider-Man and the Human Torch in a story by writer Roy Thomas and artist Ross Andru.

[6] A multi-issue time travel story arc began in issue #41 with Spider-Man and the Scarlet Witch traveling to the Salem witch trials in 1692,[7] and pushed the barriers of continuity by having Spider-Man team up with two characters who had no established connection to the mainstream Marvel Universe, Killraven and Deathlok.

[10] Byrne and his Uncanny X-Men collaborator, writer Chris Claremont worked together on several issues of Marvel Team-Up.

[22] Second Story: Black Panther Epic Collection Vol 2; Marvel Universe by John Byrne Omnibus The storyline "Spider-Man and Invincible" from Marvel Team-Up #14 was loosely adapted to "I Thought You Were Stronger", the second season finale of the Amazon Prime Video television series adaptation of Invincible, which aired April 4, 2024.

Due to Amazon and Robert Kirkman not having the rights to adapt any Marvel Universe characters from the issue to the adaptation, Robert Kirkman consulted with Amazon's legal department to "figure out a way to keep that moment somewhat intact from the comics", ultimately creating the legally distinct parody characters "Agent Spider" and "Prof Ock" to replace Spider-Man and Doctor Octopus, with the former to be voiced by "an actor who had done Spider-Man before".