This work presents an integrated geochronology study combining step-heating Ar-Ar and in-situ Rb-Sr phyllosilicate geochronology with EPMA elemental maps and U-Pb apatite geochronology in order to determine the timing and duration of regional deformation and fluid circulation processes in the Karagwe-Ankole Belt in Central Africa. The Kibuye-Gitarama-Gatumba study area (West Rwanda) forms part of the Western Domain of this Mesoproterozoic belt, where the metamorphic and deformation history, geothermometric evolution and mineralization processes (both genesis and geochronology) have been well-documented in previous studies. Our geochronological results and interpretations show the importance of thermal diffusion throughout the elevated temperature regime present in the Neoproterozoic. During the Ediacaran, metamorphism and fluid alteration in the Gatumba area was associated with deformation, as independently demonstrated by U-Pb apatite and Ar-Ar phyllosilicate geochronology. From the end of the Ediacaran until the Late Cambrian, saline fluid activity is recorded and fluid-induced (re)crystallization processes dominate the Gatumba biotite isotope record. The direct comparison between and Ar-Ar geochronology suggests a parentless ⁴⁰Ar-component is preserved during this fluid-induced (re)crystallization due to its saline, (earth) alkali-rich composition. Additionally, this multi-method approach allows us to place the history of the Western Domain of the Karagwe-Ankole belt in relation to that of the surrounding areas, i.e. the Eastern Domain and the Congo and Tanzania Cratons. Deformation and epidote-amphibolite facies metamorphism (at ~590–570 Ma), and fluid fluxes (at ~590–495 Ma) occurred in the Kibuye-Gitarama-Gatumba area after the West Gondwana Orogeny but from the onset of the East African Orogeny onwards till after the culmination of the Gondwana amalgamation, demonstrating the progressively eastward-moving orogenic front in this supercontinent assembly.