Disentangling the relative contribution of the various factors underlying Middle Palaeolithic industrial variability remains one of the foremost problems for researchers interested in Neandertal technological and behavioural adaptations. The site of Combe-Grenal (Dordogne) has figured prominently in these discussions given its long stratigraphic sequence and rich archaeological record that extends from MIS 6 to MIS 3 and contains all of F. Bordes' Mousterian facies. Departing from a strict typological approach, we provide a revised vision of the site's sequence focused on individualising lithic production systems. We investigate to what extent typologically different industries, beyond their separation imposed by the very idea of discrete Mousterian facies, nevertheless portray comparable production systems. By eschewing a chronology of the traditional Mousterian facies, our technological approach to the Combe-Grenal assemblages succeeded in identifying a clear stratigraphic succession where strictly typological approaches had previously failed. Moreover, comparison with other regional sequences shows the succession of Mousterian technological systems identified at Combe-Grenal not to be an exception in south-western France. We propose a revised chronology for the site's sequence based on a correlation of changes in the structure of regional faunal communities with independent palaeo-environmental data. Finally, comparing technological data with raw material provisioning strategies and elements of faunal exploitation, such as prey availability, provides insights concerning the interpretation of Mousterian variability and the investigation of changing patterns of Neandertal landscape use.