A new species of nototheniid fish, Cryothenia amphitreta, is described from a single gravid female collected in mid-November 2004 by divers in McMurdo Sound in the Ross Sea region of Antarctica. The new species closely resembles the only known congener, C. peninsulae, collected off the west coast of the Antarctic Peninsula, but differs substantially in pelvic-fin length (13.4 vs. 19.3–24.4% SL), total vertebrae (57 vs. 50–53), body size at maturity (261 vs. 100–144 mm), and interorbital-pit morphology. The neutrally-buoyant C. amphitreta is characterized by a wide, well-defined interorbital pit divided by a raised medial ridge, scales anterior to this depression in the interorbital region, and a dark pigmentation of the mouth, gill, and body cavity linings. This species is protected against freezing by high levels of antifreeze proteins in its body fluids. Phylogenetic reconstruction using the mitochondrial NADH dehydrogenase subunit 2 (mtND2) suggests that C. amphitreta falls within the current designation of the nototheniid subfamily Trematominae.