The highly productive waters of the Humboldt Current System (HCS) host a particular temperate ecosystem within the tropics, whose history is still largely unknown. The Pisco Formation, deposited during Mio-Pliocene times in the Peruvian continental margin has yielded an outstanding collection of coastal-marine fossils, providing an opportunity to understand the genesis of the HCS ecosystem. We present a comprehensive review, completed with new results, that integrates geological and paleontological data from the last 10 My, especially focusing on the southern East Pisco Basin (Sacaco area). We discuss the depositional settings of the Pisco Formation and integrate new U/Pb radiometric ages into the chronostratigraphic framework of the Sacaco sub-basin. The last preserved Pisco sediments at Sacaco were deposited ~ 4.5 Ma, while the overlying Caracoles Formation accumulated from ~ 2.7 Ma on...