Pesticide poisoning is widely accepted as a major public health problem in low- and middle-income countries, especially in East Africa. However, a very high proportion of unintentional poisonings are either unreported or misreported. To help fill this knowledge gap, we investigated the scale of unintentional acute pesticide poisoning (UAPP) in cotton-growing communities in Tanzania by conducting a cross-sectional survey of 1074 cotton farmers or farm workers. The findings from this study revealed a high incidence of self-reported negative health effects following occupational pesticide exposure, with 48% of respondents experiencing symptoms of UAPP within the previous 12 months. Furthermore, the substantial proportion of UAPP incidents were associated with a few highly hazardous pesticides (HHPs), particularly profenofos, lambda cyhalothrin, and co-formulations with both chlorpyrifos and cypermethrin. Of those reporting UAPP, only 6% sought medical treatment in a formal healthcare setting. The findings from this study clearly indicates an urgent need for improved pesticide regulation, the scale up of community surveillance, and the promotion of less hazardous alternatives to the use of HHPs. We provide policy recommendations and identify alternatives to HHPs for cotton pest management.