Background Plasmodium vivax malaria is one of the major infectious diseases of public health concern in Nouakchott, the capital city of Mauritania and the biggest urban setting in the Sahara. The assessment of the current trends in malaria epidemiology is primordial in understanding the dynamics of its transmission and developing an effective control strategy. Methods A 6 year (2015–2020) prospective study was carried out in Nouakchott. Febrile outpatients with a clinical suspicion of malaria presenting spontaneously at Teyarett Health Centre or the paediatric department of Mother and Children Hospital Centre were screened for malaria using a rapid diagnostic test, microscopic examination of Giemsa-stained blood films, and nested polymerase chain reaction. Data were analysed using Microsoft Excel and GraphPad Prism and InStat software. Results Of 1760 febrile patients included in this study, 274 (15.5%) were malaria-positive by rapid diagnostic test, 256 (14.5%) were malaria-positive by microscopy, and 291 (16.5%) were malaria-positive by PCR. Plasmodium vivax accounted for 216 of 291 (74.2%) PCR-positive patients; 47 (16.1%) and 28 (9.6%) had P. falciparum monoinfection or P. vivax–P. falciparum mixed infection, respectively. During the study period, the annual prevalence of malaria declined from 29.2% in 2015 to 13.2% in 2019 and 2.1% in 2020 (P < 0.05). Malaria transmission was essentially seasonal, with a peak occurring soon after the rainy season (October–November), and P. vivax infections, but not P. falciparum infections, occurred at low levels during the rest of the year. The most affected subset of patient population was adult male white and black Moors. The decline in malaria prevalence was correlated with decreasing annual rainfall (r = 0.85; P = 0.03) and was also associated with better management of the potable water supply system. A large majority of included patients did not possess or did not use bed nets. Conclusions Control interventions based on prevention, diagnosis, and treatment should be reinforced in Nouakchott, and P. vivax-specific control measures, including chloroquine and 8-aminoquinolines (primaquine, tafenoquine) for treatment, should be considered to further improve the efficacy of interventions and aim for malaria elimination.