The character has been substantially adapted from the comics into various forms of media, including films, animated series, and video games.

In December 2021, Spider-Man: No Way Home (2021) screenwriters Chris McKenna and Erik Sommers confirmed that Uncle Ben's comic book role as Peter's "moral guide" in the Marvel Cinematic Universe (MCU)—who tells him his life motto before being killed as a result of his actions—had instead been adapted to his aunt May Parker, portrayed by Marisa Tomei in five films from 2016 to 2021.

[1] Adam Scott portrays a younger Ben Parker in the Sony's Spider-Man Universe (SSU) film Madame Web (2024).

After first appearing in Strange Tales #97 (January 1962)—caring for his niece (a mermaid named Linda Brown) with his wife May—Uncle Ben returned in Amazing Fantasy #15 (August 1962)—caring for his nephew (Peter Parker / Spider-Man) with May—and was killed in the same issue.

The violent killing of Uncle Ben, done by a common street criminal, also shares multiple similarities to the death of Thomas and Martha Wayne, the parents of Batman, which sometimes is included in the saying.

[2] There have been examples of Uncle Ben remaining alive in alternative timelines, including stories featured in Marvel's What If (one of which he forces Peter to unmask in front of J. Jonah Jameson), and a storyline of the 1994 Spider-Man animated series featured a universe where Uncle Ben had never died, and Peter Parker became a successful industrialist, having never really bothered to use his powers responsibly as everything always seemed to work out for him.

This alternate Ben came to the planet Earth of regular Marvel comics (the 616 reality) as part of an evil plan devised by the Hobgoblin of 2211 to defeat the Spider-Men of different eras.

[5] Although tempted at the offer, Peter concluded that the reason Reilly had not brought Uncle Ben back on his own was that he knew that Uncle Ben would disapprove of Reilly's actions, as his plan would see everyone on Earth granted immortality, while dependent on him to supply the medication needed to stabilize their cloned bodies.

He had known his future wife, May Reilly since their high school days, but she, in turn, was naively interested in a boy who was involved in criminal activities.

Creating the costumed identity of Spider-Man for himself, Peter sought first to exploit his newfound powers as a masked wrestler and then as a television star.

The guard called for Spider-Man to stop the robber, but the nascent Spidey refused on the grounds that catching criminals was not his job.

[14] During the 2008–2009 "Dark Reign" storyline, Uncle Ben makes an appearance in the Underworld when Hercules attends the trial of Zeus, directing Amadeus Cho as he attempted to find his parents in the afterlife.

[15] In the "Amazing Grace" storyline, Ben appears as an apparition to Spider-Man while battling a horde of demons and gargoyles, telling him that his death is not Peter's or anyone's fault.

[17] When Spider-Man finally confronts Kindred during the "Last Remains" arc, he finds that Kindred had dug up the bodies of Uncle Ben, Gwen Stacy, George Stacy, Ned Leeds, J. Jonah Jameson Sr., Jean DeWolff, and Marla Jameson and sat them around a dinner table.

[18] Lee and Ditko introduced the character of "Uncle Ben" alongside "Aunt May" in the June 1962 issue of Strange Tales #97, four months before his Amazing Fantasy debut.

[19][20] A version of Ben appeared in the Mark Millar, Terry Dodson 2003 limited series, Trouble, with his brother Richie, who were involved with teenagers, May and Mary.

Peter's focus on his career prompts him to eventually leave home, simply paying Ben a percentage out of respect for their old relationship rather than any actual concern.

This Ben was eventually 'derailed' into the 616 reality by the Hobgoblin of 2211 as part of her plan against the Spider-Men of various eras, leaving him shocked when he witnessed his destroyed house and the still-living May Parker.

After this Hobgoblin was erased from history by a Retcon Bomb of her own invention, the Spider-Man of 2211 met with what he presumed to be the same Ben Parker to take him back to his own timeline.

[28] In the Marvel Noir reality, Ben Parker is a social activist who was murdered by the cannibalistic Vulture, one of the enforcer of crime lord Norman Osborn.

In the present, Ben Parker is still the managing editor of the Daily Bugle and Peter is happily married to Mary Jane Watson with two kids named Richard and May.

Ben and his close friend J. Jonah Jameson quit the Bugle upon Wilson Fisk taking it over and interfering with their investigations concerning the attack.

[42] One month later, while in a Turkish bath, Ben Parker and J. Jonah Jameson talk about another attempt on Wilson Fisk's life and the emergence of Spider-Man, which they consider a distraction used by the media.

[44] While babysitting Richard and May, Ben Parker and J. Jonah Jameson talk about calling their independent news company "The Paper".