A conspicuous paucity in gold resources in Malawi’s mineral inventory may be partially attributed to a general low resolution in the knowledge of Malawi’s geology, coupled with historical under-exploration for this important economic commodity. To address this knowledge gap, the present study focusses on developing a regional, local and microscopic understanding of the characteristics of gold occurrences in the mineralized Little Chisumbwiti river valley, located in the Kirk Range region which forms part of Southern Irumide mobile belt in southern Malawi. Regional scale interpretations are afforded by in-depth investigation of airborne geophysical data, which are then supported by ground geological mapping and by microscopic observations using optical and electron microscopy, and X-ray computed tomography (XCT). Structural mapping and regional geophysics indicate that the area has been affected by at least two periods of deformation (D1 to D2). The D1 deformation event is characterized by northwest – southeast directed crustal shortening (tentatively associated with the Southern Irumide orogeny) which produced northeast – southwest structures. Gold mineralization in the Little Chisumbwiti river valley is hosted in northeast – southwest trending quartz—sulphide vein sets, where it occurs as flakes ranging in size between 0.24 and 4 mm. The gold is associated with a paragenetically-late pyrite-chalcopyrite-sphalerite generation of sulphide precipitation, and to a lesser extent, with sericitised biotite schist wall rock. Exploration in the Kirk Range region should focus on the northeast-southwest structures, which represent potential conduits for fluid flow during the D1-related hypogene Au mineralization event, however the impacts of subsequent D2 deformation must also be considered. Locally, wall rock lithology (e.g., Fe (II)-rich biotite schists) may have an additional second order control on the siting of gold mineralization. The new insights reported in this study contribute meaningfully towards advancing the status of Malawi’s regional geology and should serve as a useful resource for future exploration efforts undertaken in the Kirk Range, and in other parts of south/central Malawi occurring within the Southern Irumide tectonic block.