The April 3, 2017 MW 6.5, Moiyabana (Botswana) earthquake occurred in the continental interior of the Nubian plate and in a seismogenic region previously considered as stable. Our objective is to combine several approaches (field and remote sensing investigations) in order to adopt a multidisciplinary strategy so as to enhance our understanding of earthquake occurrence in intraplate southern Africa. We analyse the mainshock and aftershocks sequence based on a local seismic network and local seismotectonic characteristics. The earthquake rupture geometry is constrained with more than 900 aftershocks recorded over a period of three months and from the InSAR analysis of Sentinel-1 images (ascending orbit). The mainshock (25.134 E, 22.565 S; depth 22 ± 3 km) was followed by more than 500 events of magnitude M ≥ 0.8 recorded in April 2017 including the largest aftershock (MW 4.6 on the April 5, 2017). Focal mechanism solutions of the mainshock and aftershocks display predominance of NW-SE trending and NE dipping normal faulting. Stress inversion of the focal mechanisms produced results that are compatible with a NE-SW extension under normal faulting regime. The InSAR study shows fringes (a pair of ascending images 2017-03-30 and 2017-04-11) with two lobes with 3.86 cm–5.15 cm coseismic slip on a NW-SE elongated and 40-km-long surface deformation consistent with the mainshock location and normal faulting mechanism. The modelling of surface deformation provides the earthquake rupture dimension at depth with ~50 cm maximum slip on a fault plane striking 315°, dipping 45°, −80° rake and with Mo 3.68 × 1018 Nm. Although the seismic strain rate is of low level, the occurrence of the 2017 Moiyabana earthquake, followed by an aftershock sequence in the central Limpopo Mobile Belt classifies the intraplate region as an active plate interior.