Antarctic fur seals (AFS) are an ecologically important predator and a focal indicator species for ecosystem-based Antarctic fisheries management. This species suffered intensive anthropogenic exploitation until the early 1900s, but recolonized most of its former distribution, including the southern-most colony at Cape Shirreff, South Shetland Islands (SSI). The IUCN describes a single, global AFS population of least concern; however, extensive genetic analyses clearly identify four distinct breeding stocks, including one in the SSI. To update the population status of SSI AFS, we analyzed 20 years of field-based data including population counts, body size and condition, natality, recruitment, foraging behaviors, return rates, and pup mortality at the largest SSI colony. Our findings show a precipitous decline in AFS abundance (86% decrease since 2007), likely driven by leopard seal predation (increasing since 2001, p << 0.001) and potentially worsening summer foraging conditions. We estimated that leopard seals consumed an average of 69.3% (range: 50.3–80.9%) of all AFS pups born each year since 2010. AFS foraging-trip durations, an index of their foraging habitat quality, were consistent with decreasing krill and fish availability. Significant improvement in the age-specific over-winter body condition of AFS indicates that observed population declines are driven by processes local to the northern Antarctic Peninsula. The loss of SSI AFS would substantially reduce the genetic diversity of the species, and decrease its resilience to climate change. There is an urgent need to reevaluate the conservation status of Antarctic fur seals, particularly for the rapidly declining SSI population.