The ABO blood group system is the most significant in human blood transfusion, involving antigens present on red blood cells and associated antibodies. Discovered by Karl Landsteiner in 1901, ABO typing is essential for compatibility in blood transfusions, where the presence of anti-A or anti-B antibodies must be considered. Additionally, the system includes gene inheritance principles, the Bombay phenotype, and implications for Rh factors during blood transfusions and pregnancy.