The Salas y Gómez and Nazca ridges are underwater mountain chains that stretch across 2,900 km in the southeastern Pacific and are recognized for their high biodiversity value and unique ecological characteristics. Explorations of deep-water ecosystems have been limited in this region, and elsewhere globally. To characterize community composition of mesophotic and deep-sea demersal fauna at seamounts in the region, we conducted expeditions to Rapa Nui (RN) and Salas y Gómez (SyG) islands in 2011 and Desventuradas Islands in 2013. Remote autonomous baited-cameras were used to conduct stationary video surveys between 150–1,850 m at RN/SyG (N = 20) and 75–2,363 m at Desventuradas (N = 27). Individual organisms were identified to the lowest possible taxonomic level and relative abundance was quantified with the maximum number of individuals per frame. Deployments were attributed with associated environmental variables (temperature, salinity, dissolved oxygen, nitrate, silicate, phosphate, chlorophyll-a, seamount age, and bathymetric position index [BPI]). We identified 55 unique invertebrate taxa and 66 unique fish taxa. Faunal community structure was highly dissimilar between and within subregions both for invertebrate (p < 0.001) and fish taxa (p = 0.022). For fishes, dogfish sharks (Squalidae) accounted for the greatest dissimilarity between subregions (18.27%), with mean abundances of 2.26 ± 2.49 at Desventuradas, an order of magnitude greater than at RN/SyG (0.21 ± 0.54). Depth, seamount age, broad-scale BPI, and nitrate explained most of the variation in both invertebrate (R2 = 0.475) and fish (R2 = 0.419) assemblages. Slightly more than half the deployments at Desventuradas (N = 14) recorded vulnerable marine ecosystem taxa such as corals and sponges. Our study supports mounting evidence that the Salas y Gómez and Nazca ridges are areas of high biodiversity and high conservation value. While Chile and Peru have recently established or proposed marine protected areas in this region, the majority of these ridges lie outside of national jurisdictions and are under threat from overfishing, plastic pollution, climate change, and potential deep-sea mining. Given its intrinsic value, this region should be comprehensively protected using the best available conservation measures to ensure that the Salas y Gómez and Nazca ridges remain a globally unique biodiversity hotspot.