The first successful vaccination against smallpox occurred in 1796, pioneered by Edward Jenner, an English physician. Jenner utilized material from cowpox lesions, which protected individuals from contracting smallpox. His groundbreaking work demonstrated the concept of vaccination, essentially introducing a safer form of the disease to build immunity. This method significantly decreased smallpox incidence and laid the foundational principles of immunology and vaccination. Jenner's discovery heralded the development of vaccines for various diseases, representing a monumental advancement in medical science and public health, ultimately paving the way toward the global eradication of smallpox by the late 20th century.