Born in Medellín on April 19, 1932, Botero was the second of three children of David Botero Mejía, a businessman, and Flora Angulo de Botero, a seamstress. His older brother Juan David had been born four years earlier, and his younger brother Rodrigo was born in 1936, the same year his father died.

In 1938 Botero began his primary education and continued his secondary education at the Bolívar Jesuit School.