Objective: The impact of inbreeding in the two branches of the Habsburg dynasty, the Spanish and the Austrian Habsburgs, is investigated to explain why the Spanish lineage was extinguished at the end of the 17th century and the Austrian lineage not. Methods: Kinship and inbreeding coefficients for the Habsburgs were computed from pedigree analysis. Different regression methods were used to measure the effect of inbreeding on survival from birth to 10 years of age. Results: As a consequence of the persistent consanguinity over generations, a number of Spanish and Austrian Habsburgs presented extremely high inbreeding coefficients. The mean inbreeding coefficient was 0.0790 ± 0.0169 for the Austrian Emperors and 0.1287 ± 0.0378 for the Spanish kings. A statistically significant inbreeding depression for survival to 10 years of age was detected in the two lineages (estimates of the inbreeding load were 2.985 ± 0.820 for the Austrian Habsburgs and 4.676 ± 2.416 for the Spanish Habsburgs). However, statistically significant differences between the two lineages were not detected for both inbreeding coefficient and magnitude of inbreeding depression. Conclusions: It is shown that the interaction between inbreeding and historical contingency is critical for the understanding of the downfall of the Spanish Habsburgs and the continuity of the Austrian lineage.