We report a newly discovered assemblage of talc–kyanite in an amphibolite from the Isimani Suite of the Paleoproterozoic Usagaran Belt, central Tanzania. The amphibolite is characterized by the mineral assemblage of clinoamphibole, kyanite, talc with minor rutile, quartz, dolomite, and rare barite. The high Fe3+/(Fe3++Fe2+) ratio (0.48–0.80) of clinoamphibole and the presence of sulfate (barite) indicate a very-high oxidation state during metamorphism. P–T pseudosection modelling predicts that the studied talc- and kyanite-bearing amphibolites formed at high-pressure conditions (P >~1.0 GPa). Moreover, the modelling suggests that formation of talc + kyanite + clinoamphibole at a highly oxidizing condition with CO2 fluid. This talc–kyanite association provides an index of high-pressure metamorphism of the Usagaran Belt and marks the oldest record of the talc–kyanite association in regional metamorphism in the Earth’s history.