The nail penetration of lithium-ion batteries (LIBs) has become a standard battery safety evaluation method to mimic the potential penetration of a foreign object into LIB, which can lead to internal short circuit with catastrophic consequences, such as thermal runaway, fire, and explosion. To provide a safe, time-efficient, and cost-effective method for studying the nail penetration problem, an integrated computational method that considers the mechanical, electrochemical, and thermal behaviors of the jellyroll was developed using a coupled 3D mechanical model, a 1D battery model, and a short circuit model. The integrated model, along with the sub-models, was validated to agree reasonably well with experimental test data. In addition, a comprehensive quantitative analysis of governing factors, e.g., shapes, sizes, and displacements of nails, states of charge, and penetration speeds, was conducted. The proposed computational framework for LIB nail penetration was first introduced. This framework can provide an accurate prediction of the time history profile of battery voltage, temperature, and mechanical behavior. The factors that affected the behavior of the jellyroll under nail penetration were discussed systematically. Results provide a solid foundation for future in-depth studies on LIB nail penetration mechanisms and safety design.