The invention relates to composite material structure design in aerospace structures, and provides an efficient optimization method for a variable stiffness composite material plate shell structure. The method includes the steps: performing curve fiber path accurate modeling and buckling analysis on the variable stiffness composite material plate shell structure based on an isogeometric method; building an isogeometric buckling design model of the structure; deriving total analytical sensitivity of buckling response of the variable stiffness composite material plate shell structure; efficiently optimizing fiber paths of the variable stiffness composite material plate shell structure by a gradient-based method to obtain an optimal structure meeting process manufacturing constraints. According to the structure, the carrying efficiency of the variable stiffness composite material plate shell structure can be remarkably improved, and the development period of products is greatly shortened.