Globally, over 85% of oyster reefs have been lost, and the combined effects of climate change, ocean acidification, and environmental degradation, including pollution and mangrove overharvesting, could further reduce global oyster fisheries in the coming decades. To understand the level of impact of climate change on the oyster fishery in West Africa, an expert-based vulnerability assessment to climate change was conducted for the West African mangrove oyster (Crassostrea tulipa, Lamarck 1819). Using a combination of the exposure of the oyster to climatic stressors (estuarine temperature, salinity, river flow, surface run-off, sea level rise, and estuarine circulation) together with an assessment of sensitivity to these stressors, we estimate the overall vulnerability of C. tulipa to climate change. A very high overall climate vulnerability score of 12 on a scale of 16 was calculated for C. tulipa. While the overall climate exposure score in the West African coastal region remained high, the high sensitivity of C. tulipa to hydrographic conditions of its habitat, in particular salinity, coupled with its sessile and habitat-specific nature, pushed the overall vulnerability to very high. Early life history settlement requirements, adult mobility, and sensitivity to salinity were the three most important biological and sensitivity attributes that determined the vulnerability score. By leaving each of these three sensitivity attributes out of the analysis, the overall vulnerability score was reduced to 9 (i.e., from very high to high). A negative directional effect of climate change, coupled with a low potential for change in distribution, threatens the C. tulipa fishery in a long-term adverse climate scenario. We recommend management efforts that incorporate climate resilience and adaptation practices to prioritize recruitment success, as well as the development of breeding lines with climate-resilient traits.