He started his career as Christopher Columbus's pilot, before joining Francisco Pizarro and Diego de Almagro on their conquest of Peru.

[1] Ruiz's first known job in the Americas was piloting for Lorenzo de Aldana, exploring the coastal regions of Panama.

[2] Ruiz next sailed to Ecuador, becoming the first European to explore the Santiago River, Puma Lagartos, Point Oysters, the islands of Corcovado, and Cape San Francisco – named in honor of Pizarro.

It awarded Bartolomé Ruiz the title and honors, "Hidalgo, Knight of the Golden Spur, Pilot of the South Sea," and a salary of 75,000 maravedis per year, and perpetual Regent of Tumbes.

After the Incan Emperor Atahualpa was captured at Cajamarca in 1532, Ruiz arrived with three ships to reinforce the Spanish.