Abstract Objective Over the past twenty-five years, the field of neuropsychology has expanded internationally. To date, an accurate understanding of the appropriateness of psychometric tests available in African countries remains limited despite the established need and potential benefits. Given the influence of culture on cognition the current study explores the differences in cognitive test performance between Cameroonian and American adults to add to the existing knowledge base. Methods The Cameroonian sample, 250 adults ages 22–72 (mean age = 42.91 [SD = 13.76], 52% male, mean education = 13.54 [SD = 4.58]) resided in Yaoundé, Cameroon. Participants were tested at a district center. Deidentified data from a community mental health center’s archival database comprised the American sample. An independent sample t-test was conducted to examine differences in performance between Cameroonian adults and a matched sample of American adults on selected measures. Results The results indicate significant differences between Cameroonians and Americans in cognitive performance on the WAIS-IV Digit Span [t(777) = −31.534, p = 0.013 < 0.05, d = 4.70], Stroop Word [t(823) = −1.117, p = 0.000 < 0.05, d = 13.244], Stroop Color [t(823) = −0.518, p = 0.000 < 0.05, d = 10.443], Stroop Color Word [t(823) = −14.539, p = 0.000 < 0.05, d = 8.999] subtests. Conclusion The significant variation in performance between the groups indicates the potential for culturally distinctive functioning and the need for further exploration of how test bias may manifest cross-culturally in neuropsychological assessments within Cameroon. Implications of the current findings include specific recommendations for research and practice within Cameroon to best serve this population.