The actin filament‐severing functionality of gelsolin resides in its N‐terminal three domains (G1–G3). We have determined the structure of this fragment in complex with an actin monomer. The structure reveals the dramatic domain rearrangements that activate G1–G3, which include the replacement of interdomain interactions observed in the inactive, calcium‐free protein by new contacts to actin, and by a novel G2–G3 interface. Together, these conformational changes are critical for actin filament severing, and we suggest that their absence leads to the disease Finnish‐type familial amyloidosis. Furthermore, we propose that association with actin drives the calcium‐independent activation of isolated G1–G3 during apoptosis, and that a similar mechanism operates to activate native gelsolin at micromolar levels of calcium. This is the first structure of a filament‐binding protein bound to actin and it sets stringent, high‐resolution limitations on the arrangement of actin protomers within the filament.