Flexible pavement structure design is a complex task because of the variability of design input parameters and complex failure mechanisms. Therefore, the aim of this study is to develop and implement a simplified Mechanistic-Empirical (M-E) pavement design method based on the 1993 American Association of State Highway and Transportation Officials (AASHTO), the National Cooperative Highway Research Program (NCHRP) 9-22, and NCHRP 1-37A and 1-40D projects. This simplified methodology is implemented into a computer code and a user-friendly software called “ME-PAVE”. In this methodology, only two equivalent temperatures, as per the NCHRP 9-22 project, are estimated to adjust the dynamic modulus of the asphalt layer(s) for Asphalt Concrete (AC) rutting and AC fatigue cracking prediction instead of using the hourly climatic data, as in the AASHTOWare Pavement ME. In ME-PAVE, the structural responses at critical locations in the pavement structure are determined by a Finite Element Module (FEM), which is verified by a Multi-layer Elastic Analysis (MLEA) program. To ensure that the simplified methodology is practical and accurate, the incorporated transfer functions in the proposed simplified methodology are calibrated based on the Long-Term Pavement Performance (LTPP) data. Based on statistical analyses, the built-in FEM results exhibit very similar trends to those yielded by MLEA, with a coefficient of determination, R2 of 1.0. For all practical purposes, the proposed methodology, despite all simplifications, yields acceptable prediction accuracy with R2 of 0.317 for the rut depth compared to the current practices, NCHRP 1-37A and 1-40D (R2 = 0.399 and 0.577, respectively); while the prediction accuracy for fatigue cracking with R2 of 0.382 is comparable to the NCHRP 1-40D with R2 of 0.275. Nonetheless, the standard error for both distresses is in good agreement based on the investigated data and the developed methodology. Finally, the conducted sensitivity analysis demonstrate that the proposed methodology produces rational pavement performance.