Cephalopod assemblages at the scale of the entire Mediterranean Sea were analysed using information from 2 decades of standardized scientific bottom trawl surveys. Western and eastern assemblages (6 yr of data) were compared using a combined approach of multivariate ordination techniques and non-linear regressions. These methods enabled us to distinguish assemblages and simultaneously analyse the influence of geographic, bathymetric and environmental (sea surface temperature and chlorophyll a concentration) gradients on observed community patterns. Despite few differences in species composition between sub-basins, the relative contribution of species differed. Bathymetry was the primary structural driver for the cephalopod communities of both basins, and contributed to 3 assemblages (shallow water, upper slope and middle slope). Winter temperature influenced community assemblages more strongly in the western than in the eastern basin, in contrast to a small but consistent winter productivity influence on community assemblages in both basins. Thus, the environmental parameters analysed did not cause an immediate change in cephalopod assemblages, but rather an effect lagged by several months. Differences in the relative importance of environmental drivers show that different processes operate in the 2 basins. These results demonstrate similarities and differences between Mediterranean basins regarding important cephalopod functional groups. This information should help integrative ecosystem management approaches currently used in fisheries and conservation management.