The adults of the frog Atelognathus patagonicus display phenotypic plasticity and two morphotypes, namely, “aquatic” and “littoral”, and the transition from one to the other is a reversible way of adapting to different environments. The aquatic form lives underwater associated with vegetation and rocks and has lateral skin folds and interdigital membranes. Otherwise, the littoral form lives up to a few kilometers away from the water and does not have bagginess and the interdigital membranes are reduced. Considering that morphology and function of the visual system and skin composition are characters highly associated with habitat conditions, we performed a histological comparison of the eye and skin of both aquatic and littoral morphotypes of A. patagonicus. The aquatic morphotype A. patagonicus does not have an evident character that improves vision underwater, suggesting that clues for subaquatic life could not be only visual. However, the eyelid of the littoral morph has more mucous glands than that of the aquatic morph, which is consistent with the mucus secretion of these glands and its association with terrestrial environments. Also, the skin littoral morph is more keratinized and thicker than the aquatic one, which helps to prevent desiccation. Finally, the lateral skin of the aquatic morph is highly vascularized, suggesting an increase in cutaneous respiration. This work is a starting point for understanding, in an integrative way, the different mechanisms and systems modifications in the water–land transition of A. patagonicus.