AbstractThe long‐term hydroclimatic variability in Santiago (Chile) was analysed by means of a new 481‐year (1536–2016 CE) tree‐ring reconstruction of the Standardized Precipitation Evapotranspiration Index (SPEI) of August, integrating the hydroclimatic conditions during the preceding 14 months. Results show a high frequency of extreme drought events in the late 20th and early 21st centuries, while the frequency of extreme wet events was higher in the 17th–18th centuries. The mid‐20th century represents a breaking point for the hydroclimatic history in the region, including some significant changes: (a) the interannual variability increased; (b) the wet events became less intense; (c) the extreme dry events became more frequent; and (d) the most intense dry event of the entire period was identified, coinciding with the so‐called Megadrought (2006–2016). A correlation analysis between the reconstructed SPEI and three climate indices (PDO, SOI and Niño3.4) was performed at monthly scale, considering different multi‐annual aggregations. The analysis shows diverse impacts on the hydroclimatic variability, with positive correlations between SPEI and PDO as well as Niño3.4, and negative correlations between SPEI and SOI. The most significant correlations were, overall, found at multi‐annual time scales (>7 years). Results help to better understand the current hydroclimatic changes (Megadrought) in a long‐term context.