Lithium-ion batteries (LIBs) are now widely applied to electric vehicles, such that the inevitable mechanical abuse safety problem during possible vehicle accidents has become a prominent barrier. This study initially proposes a multiphysics computational framework model that couples mechanical, thermal, and electrochemical models to describe the complete process for a single 18650 LIB cell subjected to abusive mechanical loading from initial deformation to the final thermal runaway. The designed experiments reveal the proposed model’s suitable agreement with the established multiphysics model. Parametric studies in terms of governing factors, such as state of charge, loading speed, and deformation displacement, are conducted and discussed. These studies reveal the underlying mechanism for the mechanical abuse safety of LIBs. This model can lay a solid foundation to understand the electrochemical and mechanical integrity of LIBs, as well as provide critical guidance for battery safety designs.