Droughts are amongst the most destructive natural disasters in the world. In large regions of Africa, where water is a limiting factor and people strongly rely on rain-fed agriculture, droughts have frequently led to crop failure, food shortages and even humanitarian crises. In eastern and southern Africa, major drought episodes have been linked to El Niño-Southern Oscillation (ENSO) events. In this context and with limited in-situ data available, remote sensing provides valuable opportunities for continent-wide assessment of droughts with high spatial and temporal resolutions. This study aimed to monitor agriculturally relevant droughts over Africa between 2000–2016 with a specific focus on growing seasons using remote sensing-based drought indices. Special attention was paid to the observation of drought dynamics during major ENSO episodes to illuminate the connection between ENSO and droughts in eastern and southern Africa. We utilized Tropical Rainfall Measuring Mission (TRMM)-based Standardized Precipitation Index (SPI) with 0.25∘ resolution and Moderate-resolution Imaging Spectroradiometer (MODIS)-derived Vegetation Condition ... mehrIndex (VCI) with 500 m resolution as indices for analysing the spatio-temporal patterns of droughts. We combined the drought indices with information on the timing of site-specific growing seasons derived from MODIS-based multi-annual average of Normalized Difference Vegetation Index (NDVI). We proved the applicability of SPI-3 and VCI as indices for a comprehensive continental-scale monitoring of agriculturally relevant droughts. The years 2009 and 2011 could be revealed as major drought years in eastern Africa, whereas southern Africa was affected by severe droughts in 2003 and 2015/2016. Drought episodes occurred over large parts of southern Africa during strong El Niño events. We observed a mixed drought pattern in eastern Africa, where areas with two growing seasons were frequently affected by droughts during La Niña and zones of unimodal rainfall regimes showed droughts during the onset of El Niño. During La Niña 2010/2011, large parts of cropland areas in Somalia (88%), Sudan (64%) and South Sudan (51%) were affected by severe to extreme droughts during the growing seasons. However, no universal El Niño- or La Niña-related response pattern of droughts could be deduced for the observation period of 16 years. In this regard, we discussed multi-year atmospheric fluctuations and characteristics of ENSO variants as further influences on the interconnection between ENSO and droughts. By utilizing remote sensing-based drought indices focussed on agricultural zones and periods, this study attempts to contribute to a better understanding of spatio-temporal patterns of droughts affecting agriculture in Africa, which can be essential for implementing strategies of drought hazard mitigation.