Background HIV and syphilis are common sexually transmitted infections in sub-Saharan Africa. We aimed to investigate the prevalence and distribution of active syphilis while considering HIV status, demographic characteristics, and behavioural characteristics. Methods The Population-based HIV Impact Assessment surveys used a cross-sectional, two-stage, stratified cluster sample design to collect data in Ethiopia, Tanzania, Uganda, Zambia, and Zimbabwe from 2015 to 2018. Eligible participants were aged 15 years and older and provided demographic information, behavioural information, and blood specimens for HIV and syphilis testing. Active syphilis was defined as the presence of both treponemal and nontreponemal antibodies, measured using an antigen-based rapid test. Multivariable logistic regression models with survey weights were applied. The estimated number of participants with active syphilis in each country was calculated by multiplying the survey-weighted syphilis prevalence by the corresponding participant population size from the latest national census data. The total burden across the five countries was obtained by summing these estimates. Findings 102 831 participants enrolled in the five surveys (54 583 [57<middle dot>6%] participants were female, 48 248 [42<middle dot>4%] participants were male, 9036 [9<middle dot>9%] participants were HIV positive). Population-based syphilis prevalence was 0<middle dot>9% (95% CI 0<middle dot>7-1<middle dot>1) in Tanzania and Zimbabwe, 2<middle dot>1% (1<middle dot>9-2<middle dot>4) in Uganda, and 3<middle dot>0% (2<middle dot>7-3<middle dot>4) in Zambia. Overall, an estimated 1 027 615 (95% CI 877 243-1 158 246) participants had active syphilis across the five countries (266 383 HIV-positive and 761 232 HIV-negative individuals). Syphilis prevalence was higher among people living with HIV (range from 2<middle dot>6% [95% CI 1<middle dot>1-4<middle dot>0] in Ethiopia to 9<middle dot>6% [8<middle dot>1-11<middle dot>0] in Zambia) than among those without HIV (range from 0<middle dot>8% [0<middle dot>7-1<middle dot>0] in Tanzania to 2<middle dot>1% [1<middle dot>8-2<middle dot>4] in Zimbabwe). The odds of active syphilis were higher among people living with HIV than in those who were HIV negative (adjusted odds ratio [aOR] range from 2<middle dot>5 [95% CI 1<middle dot>8-3<middle dot>4] in Uganda to 5<middle dot>9 [3<middle dot>8-9<middle dot>2] in Zimbabwe), among divorced, separated, or widowed individuals (aOR range from 1<middle dot>5 [1<middle dot>1-2<middle dot>0] in Uganda to 2<middle dot>7 [1<middle dot>7-4<middle dot>3] in Zimbabwe), and among those reporting two or more sexual partners in the previous 12 months (aOR range from 1<middle dot>1 [CI 0<middle dot>8-1<middle dot>5] in Uganda to 1<middle dot>9 [1<middle dot>1-3<middle dot>3] in Zimbabwe). Interpretation This study shows the high burden of syphilis in five sub-Saharan African countries, with a correlation between HIV and active syphilis, underscoring the need for integrated sexual health services and targeted diagnosis, prevention, and treatment strategies to address this public health challenge. Funding The President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license.