Global sea-level rise is caused, in part, by more rapid ice discharge from Antarctica, following the removal of the restraining forces of floating ice-shelves after their break-up. A trigger of ice-shelf break-up is thought to be stress variations associated with surface meltwater ponding and drainage, causing flexure and fracture. But until now, there have been no direct measurements of these processes. Here, we present field data from the McMurdo Ice Shelf, Antarctica, showing that the filling, to ~2 m depth, and subsequent draining, by overflow and channel incision, of four surface lakes causes pronounced and immediate ice-shelf flexure over multiple-week timescales. The magnitude of the vertical ice-shelf deflection reaches maxima of ~1 m at the lake centres, declining to zero at distances of <500 m. Our results should be used to guide development of continent-wide ice-sheet models, which currently do not simulate ice-shelf break-up due to meltwater loading and unloading.