The interaction between isothermal aging and the long-term reliability of fine-pitch ball grid array (BGA) packages with Sn-3.0Ag-0.5Cu (wt.%) solder ball interconnects was investigated. In this study, 0.4-mm fine-pitch packages with 300-μm-diameter Sn-Ag-Cu solder balls were used. Two different package substrate surface finishes were selected to compare their effects on the final solder composition, especially the effect of Ni, during thermal cycling. To study the impact on thermal performance and long-term reliability, samples were isothermally aged and thermally cycled from 0°C to 100°C with 10 min dwell time. Based on Weibull plots for each aging condition, package lifetime was reduced by approximately 44% by aging at 150°C. Aging at 100°C showed a smaller impact but similar trend. The microstructure evolution was observed during thermal aging and thermal cycling with different phase microstructure transformations between electrolytic Ni/Au and organic solderability preservative (OSP) surface finishes, focusing on the microstructure evolution near the package-side interface. Different mechanisms after aging at various conditions were observed, and their impacts on the fatigue lifetime of solder joints are discussed.