The signal crayfish (Pacifastacus leniusculus) was introduced to Crater Lake in 1915 and now threatens the local extinction of an endemic salamander, the Mazama newt (Taricha granulosa mazamae). More than a century after their introduction, crayfish have expanded in distribution to occupy nearly 80% of the lakeshore. Although newts remain in uninvaded areas, they are almost entirely absent in crayfish occupied areas. Abundance of benthic macroinvertebrates was dramatically reduced in locations with crayfish compared with areas of the lake where crayfish were absent. Isotopic signatures of newt and crayfish tissue confirm overlap in the diets of the two species and demonstrate their similar position in the Crater Lake food web. Mesocosm experiments conducted with newts and crayfish revealed that crayfish prey directly on newts, displace newts from cover, and generally alter newt behavior. Combined, this evidence suggests that further crayfish expansion likely will cause additional declines in newt abundance and distribution, and could lead to extinction of the unique population of newts in Crater Lake.