Damage pre-cursors based health management and prognostication methodology has been presented for electronic systems in harsh environments. The framework has been developed based on a development of correlation between damage pre-cursors and underlying degradation mechanisms in lead-free packaging architectures. The proposed methodology eliminates the need for knowledge of prior stress histories and enables interrogation of system state using the identified damage pre-cursors. Test vehicle includes various area-array packaging architectures subjected to single thermo-mechanical stresses including thermal cycling in the range of -40°C to 125°C and isothermal aging at 125°C. Experimental data on damage pre-cursors has been presented for packaging architectures encompassing flex-substrate ball grid arrays, chip-array ball grid arrays, and plastic ball grid arrays. Examples of damage proxies include, phase-growth parameter, intermetallic thickness and interfacial stress variations. Dam...