Background During the COVID-19 pandemic, national and local measures were implemented on the island of Mayotte, a French overseas department in the Indian Ocean with critical socioeconomic and health indicators. Aim We aimed to describe the COVID-19 outbreak in Mayotte from March 2020 to March 2021, with two waves from 9 March to 31 December 2020 and from 1 January to 14 March 2021, linked to Beta (20H/501Y.V2) variant. Methods To understand and assess the dynamic and the severity of the COVID-19 outbreak in Mayotte, surveillance and investigation/contact tracing systems were set up including virological, epidemiological, hospitalisation and mortality indicators. Results In total, 18,131 cases were laboratory confirmed, with PCR or RAT. During the first wave, incidence rate (IR) peaked in week 19 2020 (133/100,000). New hospitalisations peaked in week 20 (54 patients, including seven to ICU). Testing rate increased tenfold during the second wave. Between mid-December 2020 and mid-January 2021, IR doubled (851/100,000 in week 5 2021) and positivity rate tripled (28% in week 6 2021). SARS-CoV-2 Beta variant (Pangolin B.1.351) was detected in more than 80% of positive samples. Hospital admissions peaked in week 6 2021 with 225 patients, including 30 to ICU. Conclusion This massive second wave could be linked to the high transmissibility of the Beta variant. The increase in the number of cases has naturally led to a higher number of severe cases and an overburdening of the hospital. This study shows the value of a real-time epidemiological surveillance for better understanding crisis situations.