This study examines Charles Darwin's legacy and demonstrates how the principles of evolution by natural selection have transitioned from a 19th-century explanatory theory into a practical framework guiding modern biotechnology. The methodology combined a historical-analytical review of Darwin's scientific trajectory—from the voyage of the Beagle to the publication of On the Origin of Species—with an assessment of contemporary applications supported by genomic data analysis from databases such as NCBI and Ensembl and the use of bioinformatics tools including MEGA and BioEdit to construct phylogenies and compare conserved DNA regions. Results show that Darwinian understanding explains the mechanisms by which pathogens evolve and acquire antimicrobial resistance, informs vaccine design targeting conserved sequences for longer-lasting efficacy, and enables protein engineering through directed evolution to produce enzymes and antibodies with enhanced properties. Furthermore, phylogenetic analysis rooted in Darwin's tree of life has become central for predicting gene function, diagnosing disease mutations, and developing crops resistant to drought and pests. The study concludes that Darwin's legacy constitutes the theoretical and methodological cornerstone of modern biotechnology, reinforcing interdisciplinary collaboration and evidence-based experimentation, and providing an essential explanatory and predictive model for addressing health, agricultural, and industrial challenges in a rapidly changing world.