As the ban of the Pb use in electronics products is approaching due to the waste electrical and electronic equipment (WEEE) and restriction of hazardous substances (ROHS) directives, electronics companies start to deliver the products using the Pb-free solders. There are extensive databases of mechanical properties, durability properties (for both mechanical and thermal cycling), and micromechanical characteristics for Sn-Pb solders. But similar databases are not readily yet available for Pb-free solders to predict its mechanical behavior under environmental stresses. In this study, the thermo-mechanical durability of the Pb-free Sn3.8Ag0.7Cu solder is investigated by a systematic approach combining comprehensive thermal cycling tests and finite element modeling. A circuit card assembly (CCA) test vehicle was designed to analyze several design and assembly process variables when subjected to environmental extremes. The effects of mixed solder systems, device types, and underfill are addressed in the thermal cycling tests. The thermal cycle profile consisted of temperature extremes from Celsius with a dwell at hot, a dwell at cold, and a 5–10° Celsius per minute ramp. Thermal cycling results show that Sn3.8Ag0.7Cu marginally outperforms SnPb for four different components under the studied test condition. In addition, the extensive detailed three-dimensional viscoplastic finite element stress and damage analysis is conducted for five different thermal cycling tests of both Sn3.8Ag0.7Cu and Sn37Pb solders. Power law thermo-mechanical durability models of both Sn3.8Ag0.7Cu and Sn37Pb are obtained from thermal cycling test data and stress and damage analysis. The results of this study provide an important basis of understanding the thermo-mechanical durability behavior of Pb-free electronics under thermal cycling loading and environmental stresses.