Understanding top predator responses to environmental variability is key to assessing potential impacts of global warming on marine ecosystems. However, tracking environmental changes and their effects across multiple trophic levels up to predators can be difficult. Here, we related the interannual (2007–2012) acoustic occurrence of sperm whales (Physeter macrocephalus) at Ocean Station PAPA (OSP), in the offshore Gulf of Alaska (GOA), to environmental drivers within an explicit time-series modeling framework. In a model based on a combination of in-situ and remotely sensed variables, ocean heat content (HC), meridional current (V), eddy kinetic energy (EKE), strength of the permanent pycnocline (maxBVF), sea surface temperature (SST) and SST standard deviation (SSTsd) explained 51% of the variability in sperm whale presence, indicating a positive relationship between sperm whale occurrence and increased ocean heating, vertical stratification, and circulation. Sperm whale detections were anomalously high in summer 2010 and winter 2011, and anomalously low at the end of summer and winter 2008, and spring 2011. Results suggest these strongly anomalous detection events reflect a response to El Niño–Southern Oscillation (ENSO) events, with an 8-month lag. In the study area, El Niño leads to a stronger permanent pycnocline, a weakening of the Alaska Gyre, a northward expansion of the North Pacific Subarctic Frontal Zone, and a prevalence of offshore mesoscale eddies, likely favoring the abundance of squid and their predator, the sperm whale. The overall results are consistent with a scenario of increasing sperm whale occurrence at high latitudes under increased ocean warming.