Due to their flexibility, membrane structures loaded and/or supported by gas and/or fluid undergo large deformations when subjected to external loads, for example when a relatively flat membrane deflects under accumulative ponding. The most noteworthy feature during the deformation process is the loading–shape interaction since changes in the form of the structure induce changes in the loading profiles, and vice versa. Description of the hydrostatic loading is complex since the discontinuity of structural domain and fluid domain occurs with the deformation of membrane. In this paper, an interactive model dealing with accurate hydrostatic load description and nonlinear finite element analysis is employed to analysis the structural response. The hydrostatic loading is described in vectors by fluid level and loading direction in current mesh of the membrane. In case to conserve a specific volume, the free surface height is calculated with a Newton algorithm. Equivalent nodal forces evaluation on different elements are deduced especially when they are partially or fully loaded by judging the spatial relation between the element and the fluid domain, and integrating with shape functions and area coordinates in a local coordinate system. In case of multiple fluid domains, the hydrostatic load description procedure is proposed to be conducted for each fluid domain with care in identifying respective loading direction and then sum them up to get the total hydrostatic loading forces. Two numerical examples, (a) single fluid domain case: a flat membrane subjected to accumulative water loading, and (b) multiple fluid domains case: an air-inflated dam partially filled with water and loaded by lateral pressures of water, are presented to demonstrate correctness, performance and effectiveness of the proposed method in large displacement analysis of flexible membrane structures subjected to deformation dependent hydrostatic loading.