Abstract Cambarus intermontanus n. sp. is described from mountain streams in the Clear Creek basin along the Kentucky/Tennessee border between Cumberland and Pine Mountains on the Cumberland Thrust Block. The new species is morphologically most similar to Cambarus jezerinaci Thoma, 2000. It differs nevertheless from C. jezerinaci most consistently in the tuberculation of the opposable margins of the propodus. The new species possesses five or six tubercles and C. jezerinaci has four. Cambarus intermontanusn. sp. and C. jezerinaci differ from C. parvoculus Hobbs & Shoup, 1947 and C. distans Rhoades, 1944 in the thickness of the rostral margins and a more truncate rostral tip. The gonopod of C. jezerinaci has a central projection that is normally shorter than the mesial process, whereas that of C. intermontanusn. sp. is longer than the mesial process, C. distans is much shorter, and C. parvoculus is generally equal in length. The new species is genetically distinct from C. jezerinaci, C. magerae Thoma & Fetzner 2015, C. distans, and C. parvoculus differing by a 4–5% sequence divergence on average. Cambarus intermontanusn. sp. was found to be sister to a clade containing C. parvoculus, C. jezerinaci, and C. magerae.