The network of long-term meteorological observations in Southernmost Patagonia is still sparse but crucial to improve our understanding of climatic variability, in particular in the more elevated and partially glaciated Southernmost Andes. Here we present a unique 17-year meteorological record (2000–2016) of four automatic weather stations (AWS) across the Gran Campo Nevado Ice Cap (53°S) in the Southernmost Andes (Chile) and the conventional weather station Jorge Schythe of the Instituto de la Patagonia in Punta Arenas for comparison. We revisit the relationship between in situ observations and large-scale climate models as well as mesoscale weather patterns. For this purpose, a 37-year record of ERA Interim Reanalysis data has been used to compute a weather type classification based on a hierarchical correlation-based leader algorithm. The orographic perturbation on the predominantly westerly airflow determines the hydroclimatic response across the mountain range, leading to significant west-east gradients of precipitation, air temperature and humidity. Annual precipitation sums heavily drop within only tens of kilometers from ~7,500 mm a−1 to less than 800 mm a−1. The occurrence of high precipitation events of up to 620 mm in 5 days and wet spells of up to 61 consecutive days underscore the year-around wet conditions in the Southernmost Andes. Given the strong link between large-scale circulation and orographically controlled precipitation, the synoptic-scale weather conditions largely determine the precipitation and temperature variability on all time scales. Major synoptic weather types with distinct low-pressure cells in the Weddell Sea or Bellingshausen Sea, causing a prevailing southwesterly, northwesterly or westerly airflow, determine the weather conditions in Southernmost Patagonia during 68% of the year. At Gran Campo Nevado, more than 80% of extreme precipitation events occur during the persistence of these weather types. The evolution of the El Niño Southern Oscillation and Antarctic Oscillation impose intra- and inter-annual precipitation and temperature variations. Positive Antarctic Oscillation phases on average are linked to an intensified westerly airflow and warmer conditions in Southernmost Patagonia. Circulation patterns with high-pressure influence leading to colder and dryer conditions in Southernmost Patagonia are more frequent during negative Antarctic Oscillation phases.