Transgenic cotton, Gossypium hirsutum L., producing Cry1Ac and Cry2Ab2 insecticidal proteins from Bacillus thuringiensis (Bt) was first planted in Burkina Faso (West Africa) in 2008. Here, we provide the first baseline data on susceptibility of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) populations collected in West Africa (Benin, Cameroon, Nigeria, and Chad) to Cry1Ac and Cry2Ab2 toxins incorporated separately or in combination in a semisynthetic diet. For populations collected in 2006 and 2008, dose—response curves were used to estimate mortality (LC₅₀), growth inhibition (IC₅₀), and stunting (EC₅₀) of larvae. For each of these parameters, susceptibility respectively varied 44-, 23-, and 37-fold for Cry1Ac; 10-, 40-, and 25-fold for Cry2Ab2; and 37-, 11-, and nine-fold for the mixture. Country or laboratory of testing did not significantly affect susceptibility to Cry1Ac and Cry2Ab2. LC₅₀ was significantly higher in 2008 than in 2006 for Cry1Ac, possibly due to variation in experimental conditions. LC₅₀ and IC₅₀ (but not EC₅₀) were positively correlated and presented similar precision and variability across regions. However, IC could provide a more practical indicator of resistance than LC, because measuring LC and IC was equally labor intensive but estimating IC required lower amounts of toxins. Cry1Ac was two- to three-fold more toxic than Cry2Ab2 and no cross-resistance occurred among populations. Incorporation of both toxins in diet had an additive effect on mortality and growth inhibition. Our results provide a basis to establish resistance-monitoring for H. armigera before the widespread use of Bt cotton in West Africa.