Cotton is one of the most valuable materials in the world, popularly used in the clothing industry and other products. However, its production is limited by the high infestation of insect pests. A study was conducted to evaluate the effects of different biopesticides on the control of the African bollworm (Helicoverpa armigera) under cotton field conditions. Four biopesticides—namely, Eco-Bb® (Beauveria bassiana), Bb endophyte (Beauveria bassiana), Bolldex® (Nucleopolyhedrovirus), and Delfin® (Bacillus thuringiensis)—were evaluated and compared with the pyrethroid Karate® (lambda-cyhalothrin) and an untreated control against H. armigera. Field trials were conducted at the Agriculture Research Council, Rustenburg, in the North West Province of South Africa during the 2017 and 2018 cotton seasons. The results revealed that in plots sprayed with Karate® and Bolldex®, the numbers of H. armigera were significantly reduced compared to the untreated controls. Plots treated with Bolldex® had the lowest number of damaged bolls in 2017, while those treated with Karate® had the lowest number of damaged bolls in 2018. All treated plots had significantly fewer damaged bolls when compared to the controls. A seed cotton yield of 5987 kg/ha was recorded in the plots that were treated with Bolldex®—significantly higher than the yields from plots treated with Eco-Bb®, Delfin®, and Bb endophyte—in 2017. However, the yield in treatments with Eco-Bb®, Delfin®, and Bb endophyte was lower than that from the untreated controls during this season. In 2018, plots treated with Bolldex® had the highest yield, at 6818 kg/ha, which was not different from the other treatments. The highest average seed cotton yield of 6400 kg/ha was recorded in the plots treated with Bolldex®, followed by Karate®. In summary, the efficacy of different biopesticides against H. armigera varied significantly, while the synthetic pesticide (Karate®) and Bolldex® resulted in more consistent control of this pest. The results suggest that biopesticides may, however, have the potential for use in the sustainable control of cotton bollworms as part of integrated pest management programmes, although further work is required to support this hypothesis.