This fundamental contribution on time‐of‐flight secondary ion mass spectrometry polymer depth‐profiling by massive argon clusters is focused on the investigation of the influence of the Ar cluster size and the molecular weight of the investigated polymers on the efficiency of the sputtering process. For this purpose, 100‐nm thin films of polymethylmethacrylate and polystyrene, with a range of molecular weights (103–1.5 × 105 amu) spin‐coated onto Si wafers, are sputtered by 10 keV Arn+ cluster ions with selected sizes (1500, 3000 and 5000 atoms/cluster) employing Bi5+ as an analysis source. The experiments show that the sputtering yield volume (nm3/primary ion), Y, decreases with the increase of the molecular weight, Mw, for a selected cluster size, and at constant molecular weight, Y decreases with the increase in cluster size. The experimental results are in good agreement with molecular dynamics simulations and previous studies for high molecular weight PS. Furthermore, the trend of Y versus Mw seems to be related to the variation of the glass transition temperature (Tg) of the investigated polymers. Copyright © 2014 John Wiley & Sons, Ltd.