Rapid static reanalysis technology is an important tool commonly used in structural optimization design and reliability analysis. The existing static reanalysis methods are not efficient enough in solving high-rank large modification problems. To overcome this drawback, this paper proposes a new method for structural static reanalysis based on flexibility disassembly perturbation and system reduction. Firstly, a generalized flexibility disassembly perturbation technique is developed to directly compute the flexibility matrix of the modified structure. Subsequently, a new system reduction method is proposed to quickly approximate the exact solution of the modified static displacement. Even for the global large modification problem, the proposed method only requires two basis vectors to obtain very accurate calculation results. Two numerical models of statically indeterminate structures are used to verify the effectiveness and progressiveness of the method. The results show that the proposed reanalysis method has higher computational accuracy than the existing combined approximation (CA) and preconditioned conjugate gradient (PCG) methods, especially for the high-rank large modification case. A steel reticulated shell structure is further used to illustrate the application of the proposed reanalysis method in structural reliability analysis. It can be found that the proposed method significantly saves the calculation time of structural reliability analysis.