Adult sea lamprey (Petromyzon marinus) abundance in Lake Erie has remained above targets set by fishery managers since 2005, possibly due to increased recruitment in the St. Clair-Detroit River System (SCDRS). Sea lamprey recruitment in the SCDRS poses an enormous challenge to sea lamprey control and assessment in Lake Erie because the SCDRS contains no dams to facilitate capture and discharge is at least an order of magnitude larger in the SCDRS than most other sea lamprey-producing tributaries in the Great Lakes. As a first step toward understanding population size, spatial distribution, and spawning habitat of adult sea lampreys in the SCDRS, we used acoustic telemetry to determine where sea lampreys ceased migration (due to spawning, death, or both) among major regions of the SCDRS. All tagged sea lampreys released in the lower Detroit River (N = 27) moved upstream through the Detroit River and entered Lake St. Clair. After entering Lake St. Clair, sea lampreys entered the St. Clair River (N = 22), Thames River (N = 1), or were not detected again (N = 4). Many sea lampreys (10 of 27) were last observed moving downstream (“fallback”) but we were unable to determine if those movements occurred before or after spawning, or while sea lampreys were dead or alive. Regardless of whether estimates of locations where sea lampreys ceased migration were based on the most upstream region occupied or final region occupied, most sea lampreys ceased migration in the St. Clair River or Lake St. Clair. Results suggest that spawning and rearing in the St. Clair River could be an important determinant of sea lamprey recruitment in the SCDRS and may direct future assessment and control activities in that system.