<p>Norovirus can cause severe and potentially fatal gastroenteritis in infants. Mucosal vaccination of breastfeeding women may promote infant protection by enriching antibody responses in consumed breast milk. Here, we report a double-blind, placebo-controlled phase 1 trial in South Africa (SANCTR: DOH-27-072023-7893) to evaluate a single-dose oral bivalent vaccine against norovirus genotypes GI.1 and GII.4 in post-partum breastfeeding women. Safety and reactogenicity (primary outcome), breast milk and serum norovirus-specific antibodies (primary outcome), and passive transfer of antibodies to infants as measured in infant stool (exploratory outcome) were assessed. The vaccine was safe and well tolerated with similar reports of mild or moderate adverse events between placebo (<i>n</i> = 16) and vaccine groups (5 × 10¹⁰ or 1 × 10¹¹ IU/genotype, <i>n</i> = 30/group). Functional norovirus-specific breast milk and serum antibodies were significantly enriched in vaccinated groups. Norovirus-specific IgA in infant stool increased post-vaccination and positively correlated with breast milk IgA, indicating passive transfer. Thus, oral vaccination of breastfeeding women generates robust mucosal and systemic functional maternal antibodies. Our study presents a promising vaccination strategy to provide mucosal anti-norovirus immunity to infants.</p>