Abstract Background Outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across Africa. We conducted a serological survey of polio antibodies in high–polio risk areas of Niger to assess risk of poliovirus outbreaks. Methods Children between 1 and 5 years of age were enrolled from structures randomly selected using satellite imaging enumeration in Diffa Province, Niger, in July 2019. After obtaining informed consent, dried blood spot cards were collected. Neutralizing antibodies against 3 poliovirus serotypes were detected using microneutralization assay at the Centers for Disease Control and Prevention. Results We obtained analyzable data from 309/322 (95.9%) enrolled children. Seroprevalence of polio antibodies was 290/309 (93.9%), 272/309 (88.0%), and 254/309 (82.2%) for serotypes 1, 2, and 3, respectively. For serotypes 1 and 2, the seroprevalence did not significantly change with age (P = .09 and P = .44, respectively); for serotype 3, it increased with age (from 65% in 1–2-year-olds to 91.1% in 4–5-year olds; P < .001). We did not identify any risk factors for type 2 seronegativity. Conclusions With type 2 seroprevalence close to 90%, the risk of emergence of new cVDPV2 outbreaks in Niger is low; however, the risk of cVDPV2 importations from neighboring countries leading to local transmission persists. Niger should maintain its outbreak response readiness capacity and further strengthen its routine immunization.