North Africa is an intricate biogeographical region at the crossroads of immigration waves from tropical Africa and Asia. Species confined between various barriers (Atlas Mountains, arid environments such as the Sahara in the south, water masses such as the Mediterranean Sea in the north, and the Atlantic Ocean in the west) were generally forced to adapt locally to environmental changes instead of tracking their habitat by shifting their distribution area. The present study aims at providing first insight into the evolution of the genus Mus, and more specifically of the western Mediterranean species Mus spretus in this area. The study relies on the abundant Late Pleistocene and Middle Holocene fossil assemblage from the El Harhoura 2 cave (Rabat-Témara, Morocco). This exceptional record was studied using geometric morphometrics applied to first upper and lower molars, constituting the most informative and best preserved fossil remains for such small rodents. Two main issues were addressed. (1) Geometric morphometrics was used to clarify taxonomic status and phylogenetic relationships among fossil and modern species in this area. Morphometric analysis revealed good discrimination of most modern and fossil species but failed to document intermediate forms tracing anagenetic evolution. Not mutually exclusive, the occurrence of complex processes of morphological evolution in this genus such as parallel evolution and the action of stabilizing selection may make it difficult to translate patterns of morphological evolution into phylogenetic conclusions. (2) The record was shown to document a sequence of intraspecific evolution of M. spretus. The morphology of the molars through the fossil record of El Harhoura 2 was surprisingly stable despite extensive modern variation. The limited temporal variation largely failed to correlate to palaeoenvironmental proxies. The mouse fossil record at El Harhoura 2 thus presents an intriguing case of morphological stasis despite extensive environmental changes. This long-term stability may have been recently perturbed by anthropogenic factors including landscape changes and introduction of various competitors and predators, leading to a size reduction.