Objective: To determine population-based estimates of coronavirus disease 2019 (COVID-19) in a densely populated urban community of Karachi, Pakistan. Methods: Three cross-sectional surveys were conducted in April, June and August 2020 in low- and high-transmission neighbourhoods. Participants were selected at random to provide blood for Elecsys immunoassay for detection of anti-severe acute respiratory syndrome coronavirus-2 antibodies. A Bayesian regression model was used to estimate seroprevalence after adjusting for the demographic characteristics of each district. Results: In total, 3005 participants from 623 households were enrolled in this study. In Phase 2, adjusted seroprevalence was estimated as 8.7% [95% confidence interval (CI) 5.1–13.1] and 15.1% (95% CI 9.4–21.7) in low- and high-transmission areas, respectively, compared with 0.2% (95% CI 0–0.7) and 0.4% (95% CI 0–1.3) in Phase 1. In Phase 3, it was 12.8% (95% CI 8.3–17.7) and 21.5% (95% CI 15.6–28) in low- and high-transmission areas, respectively. The conditional risk of infection was 0.31 (95% CI 0.16–0.47) and 0.41 (95% CI 0.28–0.52) in low- and high-transmission neighbourhoods, respectively, in Phase 2. Similar trends were observed in Phase 3. Only 5.4% of participants who tested positive for COVID-19 were symptomatic. The infection fatality rate was 1.66%, 0.37% and 0.26% in Phases 1, 2 and 3, respectively. Conclusion: Continuing rounds of seroprevalence studies will help to improve understanding of secular trends and the extent of infection during the course of the pandemic.