We implemented a sero-epidemiological survey of SARS-CoV-2 antibodies in an age-stratified sample of people in Thailand. We used two-stage sampling employing stratified random sampling with official residence lists to recruit 1,200 people in three age strata in Bangkok, Chiang Mai, Nakhon Phanom and Phuket provinces. Serum was screened for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA) and microneutralization assay. We collected symptom and vaccination data weekly and tested participants who met a COVID-19-like illness (CLI) case definition by rRT-PCR. Serum for SARS-CoV-2 antibodies was collected and tested again in January 2022. We estimated vaccine effectiveness using multi-level Poisson regression with propensity score stratification to control for differences in healthcare-seeking behavior. Of 1,200 people enrolled in January 2021, 5 (0.4%; 95% confidence interval 0.16–1.16) had antibody detected by ELISA at baseline, and none tested positive by microneutralization. From January 2021 to January 2022, 23% of participants (278/1,200) reported CLI and 18% of CLI cases (50/278) tested positive for SARS-CoV-2 by rRT-PCR. In January 2022, 87% of participants (955/1,101) had SARS-CoV-2 antibodies detected by ELISA. Ninety-eight percent (1,034/1,045) received at least one dose of COVID-19 vaccine and did not get infection. Vaccine effectiveness against hospitalization was 72% for two doses and 98% for three doses of any vaccine. Low SARS-CoV-2 seroprevalence in 2021 suggests that Thailand successfully prevented COVID-19 infections through non-pharmaceutical interventions during the first year of the pandemic. High seroprevalence in 2022 was driven by vaccination.