Julio Mario Santo Domingo was born on October 16, 1923, in Panama City, Panama, to Mario Santo Domingo and Beatriz Pumarejo de Vengoechea, the youngest of their four children; his older siblings were Beatriz Alicia, Cecilia, and Luis Felipe.

His father was a banker, described as austere and disciplined, who made a fortune buying companies weakened during the Great Depression; his mother, from a rich and influential family, was first cousin of Alfonso López Pumarejo who was twice President of Colombia.

[4] On May 26, 1980, President Julio César Turbay Ayala appointed Santo Domingo to be the first Ambassador of Colombia to China.

He presented his Letters of Credence to Ulanhu, Vice Chairman of the Standing Committee of the National People's Congress, in Beijing on February 17, 1981.

In 2008, Andrés married socialite Lauren Davis (founder of the online fashion retailer Moda Operandi).