We present the results of an archaeoastronomical analysis of structures dating from the Inca and early colonial periods in the Mapocho River basin, Chile. Our purpose is to show possible continuities or ruptures in the creation and management of architectural and natural spaces, particularly those linked to the observation of astronomical phenomena with ceremonial and calendrical significance in the Andean world. We focus on Santiago, where we undertook topographical and horizon survey work at the Main Square, Metropolitan Cathedral, San Francisco Church and Santa Lucía Hill, and evaluate documentary and ethnographic sources. Using models developed in cultural astronomy and landscape archaeology, we found these places were ancient observation spots for the Sun and Moon around the solstices, equinoxes and lunar standstills. Sightlines (ceques) may have connected these places to potentially sacred elements of the environment from a central point located in the Main Square (haukaypata).