As he is in the 1987 series, Leatherhead is a dangerous foe to the Turtles. He appears as a boss character in each game he appears in, always employing weapons in addition to his natural implements of destruction.
Leatherhead functions as the game's fifth boss, wielding a spread gun and bashing the Turtles with his tail. Upon his energy dropping low enough, he will begin rushing at the opponent and attempting to perform a chokehold.
Leatherhead is the boss of "Bury My Shell At Wounded Knee". He is standing with his hat down at the end of the train, and attacks the Turtles when they approach. In the SNES version he crawls in from the left side of the screen. He wields large knives, stabbing with them and flinging them at the Turtles, and will often rush on all fours, flapping his jaws in an attempt to bite them. He will also kick. In the SNES version instead of stabbing and kicking, he will occasionally, spin the Turtles across the screen with his tail, or punch them. He will also sometimes throw out lobsters.
In Re-Shelled, Leatherhead is given a major redesign - the most drastic one of any character in the game. Unlike the original version, in which he looked like his 1987 incarnation, Leatherhead looks much more menacing and realistic, with a tan vest and no hat. Instead of standing on the train when the Turtles arrive at the end, he is seen running to catch up to the train, taunting them before leaping on board. Like the arcade version he also kicks and stabs at the Turtles instead of punching them.
The first boss of the game is Leatherhead, using his sprite from Turtles in Time. He uses the rush and knives from that game. Leatherhead returns in The Gauntlet level, with a complete recolor, including purple skin.
Leatherhead is an unlockable 2-star character, classified as Tank/Trickster. Although he makes multiple appearances as a boss, the cutscenes include dialogue that suggests the existence of a fake Leatherhead who antagonizes the Turtles until the real Leatherhead appears.