Anoxia can restrict species establishment in aquatic systems and the artificial promotion of these conditions can provide an effective control strategy for invasive molluscs. Low abundances (2–20 m−2) of the nonnative bivalve, Asian clam (Corbicula fluminea), were first recorded in Lake Tahoe, CA–NV in 2002 and by 2010 nuisance-level population densities (>10,000 m−2) were observed. A non-chemical control method using gas impermeable benthic barriers to reduce dissolved oxygen (DO) concentrations available to C. fluminea was tested in this ultra-oligotrophic natural lake. In 2009, the impact of ethylene propylene diene monomer (EPDM) sheets (9 m2, n = 6) on C. fluminea beds was tested on 1–7 day intervals over a 56 day period (August–September). At an average water temperature of 18 °C, DO concentrations under these small barriers were reduced to zero after 72 h resulting in 100 % C. fluminea mortality after 28 days. In 2010, a large EPDM barrier (1,950 m2) was applied to C. fluminea populations for 120 days (July–November). C. fluminea abundances were reduced over 98 % after barrier removal, and remained significantly reduced (>90 %) 1 year later. Non-target benthic macroinvertebrate abundances were also reduced, with variable taxon-specific recolonization rates. High C. fluminea abundance under anoxic conditions increased the release of ammonium and soluble reactive phosphorus from the sediment substrate; but levels of unionized ammonia were low at 0.004–0.005 mg L−1. Prolonged exposure to anoxia using benthic barriers can provide an effective short term control strategy for C. fluminea.