Reduced vaccination uptake is a growing and global public health concern. There is limited knowledge about the effect of maternal mental illness (MMI) on rates of childhood vaccination. This retrospective cohort study examined 479,949 mother-baby pairs born between 1993 and 2015 in the Clinical Practice Research Datalink (CPRD GOLD), a UK-based, primary health-care database. The influence of MMI on children's vaccination status at two and five years of age was investigated using logistic regression adjusting for sex of the child, child ethnicity, delivery year, maternal age, practice level deprivation quintile and region. The vaccinations were: 5-in-1 (DTaP/IPV/Hib) and first dose MMR by the age of two; and all three doses of 5-in-1, first and second dose of MMR vaccines by the age of five. Exposure to MMI was defined using recorded clinical events for: depression, anxiety, psychosis, eating disorder, personality disorder and alcohol and substance misuse disorders. The likelihood that a child completed their recommended vaccinations by the age of two and five was significantly lower among children with MMI compared to children with mothers without mental illness [adjusted odds ratio (aOR) 0.86, 95% CI 0.84-0.88, p < 0.001]. The strongest effect was observed for children exposed to maternal alcohol or substance misuse (at two years aOR 0.50, 95% CI 0.44-0.58, p < 0.001). In the UK, an estimated five thousand more children per year would be vaccinated if children with MMI had the same vaccination rates as children with well mothers. Maternal mental illness is a hitherto largely unrecognised reason that children may be missing vital vaccinations at two and five years of age. This risk is highest for those children living with maternal alcohol or substance misuse.