NF616 is a nominal 9Cr ferritic–martensitic steel that is amongst the primary candidates for cladding and duct applications in the Sodium-Cooled Fast Reactor, one of the Generation IV nuclear energy systems. In this study, an in situ investigation of the microstructure evolution in NF616 under heavy ion irradiation has been conducted. NF616 was irradiated to 8.4dpa at 50K and to 7.6dpa at 473K with 1MeV Kr ions. Nano-sized defects first appeared as white dots in dark-field TEM images and their areal density increased until saturation (∼6dpa). Dynamic observations at 50K and 473K showed appearance and disappearance of TEM-visible defect clusters under irradiation that continued above saturation dose. Quantitative analysis showed no significant change in the average size (∼3–4nm) and distribution of defect clusters with increasing dose at 50K and 473K. These results indicate a cascade-driven process of microstructure evolution under irradiation in these alloys that involves both the formation of TEM-visible defect clusters by various degrees of cascade overlap and cascade induced defect cluster elimination. According to this mechanism, saturation of defect cluster density is reached when the rate of defect cluster formation by overlap is equal to the rate of cluster elimination during irradiation.