The Aswa Shear Zone (ASZ) is a major NW–SE trending structure of over 1000 km length in East Africa. In Uganda, the ASZ is a steeply NE-dipping, up to 11 km wide mylonitic shear zone that shows multiple stage brittle reactivation. On outcrop-scale, the fabric in the ASZ is characterized by a well-developed NW–SE striking and subvertical or steeply NE or SW dipping mylonitic foliation and a subhorizontal to moderately NW- or SE-plunging stretching lineation. Sinistral kinematics and fabric are very consistent along strike. The strain is heterogeneously distributed and partitioned into lens-shaped lower strain zones dominated by folding and characterized by pure shear, which are surrounded by high strain zones, some of them thick ultramylonites, with intense simple shear combined with flattening and strong transposition of pre-existing fabrics. Ductile shearing occurred during bulk E–W shortening, commenced at amphibolite facies conditions and continued with similar kinematics at greenschist and even lower grade conditions. A number of (sub-)parallel shear zones occur to the NE and SW of the main zone at a distance of up to 20–45 km. They show similar fabrics and kinematics and are thus related to activity along ASZ reflecting strain partitioning into simple shear and pure shear domains on a regional scale.Samples of mylonitic gneisses from the shear zone have been analyzed with U–Pb LA-MC-ICPMS and show Neoarchaean crystallisation ages between 2.66 and 2.61 Ga. Timing of ductile sinistral shearing is poorly constrained by lower intercept ages of 686 ± 62 and 640 ± 44 Ma. The fabric and structural relationship of the ca. 660 Ma Adjumani Granite exposed in the northern segment of ASZ suggest that the age of shear activity can be further limited to ca. 685 and 655 Ma.The Aswa Shear Zone is interpreted as an intra-cratonic, crustal-scale structure close to the northeastern margin of the Congo Craton, possibly inherited from previous continental extension. Early Aswa Shear Zone activation is linked to underthrusting of the Congo Craton and coeval high-grade metamorphism and intense deformation in the orogen interior. During E–W convergence between ca. 690 and 650 Ma, the NE-dipping ASZ was activated as an oblique ramp leading to deflection of the transport direction and concentration of non-coaxial strain and sinistral shear along the shear zone system. During progressive convergence, between ca. 645 and 620 Ma, sinistral shearing along ASZ changed to ductile–brittle deformation mechanisms, while thrusting took place in Pan-African belts in eastern and western Uganda. Late-orogenic brittle sinistral reactivation of the ASZ can be regarded as the result of continent collision and closure of the Mozambique ocean further to the east, that potentially caused lateral escape manifested in NW–SE striking sinistral shear zones in Kenya and the southern Arabina-Nubian Shield between 620 and 570 Ma.