Through silicon via (TSV) is the key technology used in 2.5-D and 3-D packaging. Evaluating the reliability of products using this new technology has been challenging because of complex environmental factors. The aim of this paper was to design and implement a systematic reliability experiment to test self-designed TSV samples under the combinations of several different environmental variables. The Weibull distribution model was used to extract parameters from the experimental data for the statistical evaluation of TSV reliability. After analyzing the Weibull parameters, the environmental stresses that accelerate TSV unreliability were identified and compared, and a simple empirical unreliability equation was proposed. In addition, we observed that using a power law was an effective mean on making TSV reliability curve fittings. Failure analyses by optical microscopy, scanning electron microscopy, and energy dispersive spectrometer were finally reported.