The AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG) pavement performance models and the associated AASHTOWare® pavement design software of DARWin-ME are nationally calibrated using design inputs and distress data largely from the national Long-Term Pavement Performance (LTPP). Further calibration and validation studies are necessary for local highway agencies’ implementation by taking into account local materials, traffic information, and environmental conditions. This study aims to improve the accuracy of MEPDG/ DARWin-ME pavement performance predictions for Iowa jointed plain concrete pavements (JPCPs) through local calibration of MEPDG prediction models. The accuracy of the nationally calibrated MEPDG prediction models for Iowa conditions was evaluated. The local calibration factors of MEPDG performance prediction models were identified using both linear and nonlinear optimization approaches. The local calibration improved the accuracy of JPCP performance predictions. A comparison of MEPDG predictions with those from DARWin-ME was performed to assess if the local calibration coefficients determined from MEPDG version 1.1 software are acceptable in DARWin-ME, which has not been addressed before. Few differences are observed between DARWin-ME and MEPDG with national and local calibrated models for faulting and transverse cracking predictions for JPCP but not for International Roughness Index (IRI). With the use of locally calibrated JPCP IRI prediction model for Iowa conditions, the prediction differences between DARWin-ME and MEPDG are reduced. Finally, recommendations are presented on the use of identified local calibration coefficients of DARWin-ME/MEPDG for Iowa JPCPs.