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Abstract The recent statistics suggests that over 60% of active Cenozoic subduction initiation (SI) cases are related to the strike‐slip fault. A number of previous studies have shown that the lithospheric weak zone is a necessary condition for the SI. However, the direct effect of strike‐slip motion on lithospheric weakening and SI has rarely been investigated in numerical models due to the challenge of complex 3D boundary conditions. In this study, a new 3D model has been built with both strike‐slip and compression boundary conditions. The model results indicate that the compression at a strike‐slip boundary provides a favorable condition for the SI, with producing and maintaining a lithospheric‐scale weak zone that facilitates strain localization and SI. In addition, the high strike‐slip velocity and buoyant overriding plate contributes to the SI of young oceanic plate. This mechanism satisfies a large number of natural SI cases in the Cenozoic.