Background: Analysis of morphological variation in archipelagos has been essential to understand the evolution of terrestrial vertebrates. In particular, these natural scenarios allow to assess morphological changes experienced by insular fauna compared to their mainland counterparts. In mammals, morphological changes of insular forms have been observed in size and shape of body and cranial traits. The southern Patagonia of Chile represents a unique scenario to analyze morphological variation in two of the most widely distributed small rodents along western southern South America: Abrothrix olivacea and Oligoryzomys longicaudatus. Methods: We applied linear and three-dimensional geometric morphometric tools to analyze the variation in cranial morphology of A. olivacea (N = 80) and O. longicaudatus (N = 49). Sampled localities were distributed in the mainland and islands of the Fuegian archipelago in Chilean Patagonia. Standard multivariate methods, as Principal Components Analysis, and Logistic Regression models were carried out to evaluate differences in size and shape of crania. Results: We detected higher levels of morphological variation in the crania of A. olivacea if compared to O. longicaudatus. The variation was associated to cranial size instead of shape. We observed significant differences between insular and mainland individuals in A. olivacea, being the cranium size of this species significantly bigger on islands. Indeed, specimens of A. olivacea from "Isla Wellington", exhibited the higher increment in cranium size compared to any other mainland and insular site sampled for this species. In contrast, insular and mainland forms of O. longicaudatus did not show significant differences in cranial morphology. Conclusions: We suggest that the patterns of morphological variation observed in these two small rodents along Patagonia, could be explained in terms of the historical biogeography of the region, and the different ecological features of the studied species.