Interfacial mechanical properties have a great influence on the overall mechanical performance of graphene/flexible substrate composite structure. Therefore, it is necessary to study interfacial shear stress transfer between graphene and flexible substrate. In this paper, a two-dimensional nonlinear shear-lag model (2D model) is presented. Taking the effects of Poisson’s ratio of the graphene and substrate into consideration, the bidirectional interfacial shear stress transfer between graphene and flexible substrate subjected to uniaxial tension is investigated by the 2D model when the Poisson’s ratio of substrate is larger than that of graphene. In the elastic bonding stage, the semi-analytical solutions of the bidirectional normal strains of the graphene and bidirectional interfacial shear stresses are derived, respectively, and their distributions at different positions are illustrated. The critical strain for interfacial sliding is derived by the 2D model, and the results show that the critical strain has a micron-scaled characteristic width. The width size of graphene has a significant influence on the critical strain when it is less than the characteristic width, but the size effect can be ignored when the width of graphene is larger than the characteristic width. In addition, the Poisson’s ratio of substrate can also affect the critical strain. Based on the 2D model, the finite element simulations are made to investigate the distribution of graphene's normal strains and interfacial shear stresses in the interfacial sliding stage. Furthermore, compared with the results obtained via one-dimensional nonlinear shear-lag model (1D model), the distributions of graphene’s normal strains and interfacial shear stresses calculated by 2D model show obvious bidimensional effects both in the elastic bonding stage and in the interfacial sliding stage when the width of graphene is large. There exists a compression strain in the graphene and a transverse (perpendicular to the tensile direction) shear stress in the interface, which are neglected in the 1D model. And the distributions of graphene’s tensile strain and longitudinal (along the tensile direction) interfacial shear stress are not uniform along the width, which are also significantly different from the results of 1D model. Moreover, the critical strain for interfacial sliding derived by the 2D model is lower than that obtained by the 1D model. However, when the width of graphene is small enough, the 2D model can be approximately replaced by the 1D model. Finally, by fitting the Raman experimental results, the reliability of the 2D model is verified, and the interfacial stiffness (100 TPa/m) and shear strength (0.295 MPa) between graphene and polyethylene terephthalate (PET) substrate are calculated.