Background Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011. Methods and findings Twenty-four villages, including 2,301 children aged 3–59 months and 2,245 aged 5–9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5–9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5–9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5–9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5–9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives. Conclusions In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine. Trial registration www.clinicaltrials.gov NCT01449045. Author summary Why was this study done? Seasonal malaria chemoprevention (SMC) is recommended for children under 5 years of age for up to 4 months of the year in the Sahel and sub-Sahel, but could be useful in older children and in areas with a longer transmission season. This study was done in south-east Senegal—where the main malaria transmission season lasts for 5 months and there is a high burden of malaria in the under-10 age group—to determine the effectiveness of SMC delivered for 5 months to children under 10 years of age by community health workers (CHWs) who were also providing community case management for malaria. What did the researchers do and find? Twenty-four villages that had a resident CHW providing community case management for malaria were randomised: In 12 of the villages the CHW was trained to administer SMC once a month for 5 months during the transmission season to all children aged between 3 months and 10 years, while the other 12 villages did not have SMC. Malaria cases confirmed by rapid diagnostic test (RDT) were recorded by the CHWs. At the end of the transmission season, children were surveyed to measure their haemoglobin concentration and to check for the presence of malaria parasites. SMC was associated with 111 fewer malaria cases per 1,000 children per month in children under 5 years of age and 101 fewer cases per 1,000 children per month in children aged 5–9 years as compared with community case management alone. SMC was associated with a reduction in the percentage of children (in both age groups) with anaemia at the end of the transmission season of 18%, and a reduction in the percentage of children with malaria parasitaemia of 73%, compared to community case management alone. The study did not find a reduction in mortality and did not measure the impact of SMC on severe malaria. What do these findings mean? SMC can be administered effectively for 5 months in children up to the age of 10 years, the treatments are well tolerated, and high coverage can be achieved. Twelve countries now have SMC programmes, with SMC provided for 3 or 4 months to children under 5 years of age (with the exception of Senegal, where children under 10 years are included). The findings of this study indicate that SMC could be administered over a longer period and/or to a wider age group. The strategy could be adapted depending on local epidemiology, to increase the impact on malaria