Gastrointestinal infections significantly impact African low- and middle-income countries, although, accurate data on acute gastrointestinal illness (AGI) for all ages are lacking. This study aimed to describe the epidemiology of AGI in Ethiopia, Mozambique, Nigeria, and Tanzania. A population survey was conducted in one urban and one rural site per country, from 01 October 2020 to 30 September 2021, using web-based and face-to-face tools (n = 4417). The survey tool was adapted from high-income countries, ensuring comparability through an internationally recommended AGI case definition. Ethiopia had the highest AGI incidence (0.87 episodes per person-year), followed by Mozambique (0.58), Tanzania (0.41), and Nigeria (0.34). Age-standardized incidence was highest in Mozambique (1.46) and Ethiopia (1.25), compared to Tanzania (0.58) and Nigeria (0.33). The 4-week prevalence was 6.4% in Ethiopia and 4.3% in Mozambique, compared to 3.1% in Tanzania and 2.6% in Nigeria. AGI lasted an average of 5.3 days in Ethiopia and 3.0 to 3.4 days elsewhere. Children under five had 4.4 times higher AGI odds (95% CI: 2.8, 6.7) than those aged 15-59. The study provides empirical data on the incidence and demographic determinants of AGI in these four countries.