The story evolves around fearless muscular anti hero bounty hunter superhero Lobo the Duck and his shape shifting canine sidekick Impossible Dawg, who are investigating the murders of several Amalgam Comics superheroes, including:
Lobo only agrees to find the murderer(s) as the aforementioned heroes had paid him up-front, and soon begins the investigation. Lobo fights his way through Gold Kidney Lady, Doctor Bongface and various other supervillains before he realizes that the end of the world is about to begin, and only he can stop it. (The fate of Lobo the Duck was not revealed, as Lobo the Duck #2 was cancelled before story drafting could be completed).
Throughout the story, Lobo is accompanied by his pet, Impossible Dawg (an amalgam of Impossible Man from Marvel Comics and Dawg from DC Comics), who constantly changes into characters from the Marvel and DC universes in varying shots, including:
- The Flash
- The Thing
- Kyle Rayner
- Garko the Man-Frog (A one-off Howard the Duck foe)
- The Spectre
- Wonder Woman
- It was decided that Lobo the Duck had taken place outside of Amalgam Comics continuity in order to please fans who were otherwise upset with the deaths of the major heroes at the beginning of the book.
- When Lobo is speaking to Jonas Turnip, some graffiti on the wall reads Daphy Was Here. This is a reference to Looney Tunes character Daffy Duck. A similar gag can be seen earlier when Bevarlene enters the Diner. High on the wall, some graffiti reads: For a good time, call Huey, as a reference to Huey, Dewey, and Louie.
- Lobo the Duck was previously mentioned several times in Bat-Thing #1, perhaps as a prelude to Lobo's debut.
- In the Supervillain Directory given to Lobo at the Diner, one of the villains listed is "The Waco Kid", a character from the Mel Brooks film, Blazing Saddles, who was played by Gene Wilder.