Introduction: Malaria remains to be a major cause of morbidity and mortality in the developing world especially sub-Saharan Africa resulting in 190-311 million annual cases and about 1 million deaths worldwide, about 90% of which occur in sub-Saharan Africa especially in children below five years of age. Naturally acquired immunity develops as a function of age and exposure to Plasmodium falciparum antigens. Longitudinal studies of NAI in endemic areas to validate putative vaccine candidates usually precede clinical trials of selected malaria vaccines. Methods: A cohort study was conducted in 200 children aged between 6 months and 10 years in Tanga, Tanzania to determine natural acquisition of antibodies against malaria-specific antigens AMA-1 and MSP-119 and how they associate with malaria-related morbidity in children. Followed-up was done for six months after baseline data and blood sample collection. Antibody levels were determined using indirect ELISA and data analysed by stata. Results: The mean age was 5.6 years and mean haemoglobin level was 11.8g/dl. Baseline malaria prevalence was 10.5% but there were no malaria cases during follow-up. Anti-AMA antibody levels were higher compared to anti MSP-119 and the proportion of responders to AMA-1 was higher than MSP-119 (p < 0.05 for total IgG, IgG2, IgG3 and IgG4). Generally, antibody responses were found to increase with age while the risk of anaemia decreased with age. Conclusion: Natural acquisition of antibodies to malaria antigens increase with age and may protect against malaria-related morbidity. In this era of declining malaria, further research is needed to address malaria morbidity and immunity aspects and more efforts should be directed towards elimination of malaria through integrated approach to malaria management.