The north‐dipping Hout River Shear Zone (HRSZ), which marks the boundary between the high‐grade Limpopo Complex in its hanging wall and the low‐grade granite‐greenstone terrane of the Kaapvaal Craton in South Africa in its footwall, is a deep‐crustal shear zone that controlled emplacement of hot Limpopo Complex granulites over and against low‐grade granite‐greenstones during exhumation at ~2.72–2.62 Ga. This major shear zone controlled migration of large volumes of hydrous fluids released during devolatilization of underthrusted greenstones that infiltrated into hot overlying granulites, establishing a retrograde anthophyllite‐in isograd and associated zone of retrograde rehydrated granulite that bounds the Limpopo Complex in the south. Here, we report new petrological data based on mineral equilibrium modelling of amphibolites from the Rhenosterkoppies Greenstone Belt (RGB) located in the immediate footwall of the HRSZ and discuss evidence that these rocks also interacted with high‐temperature fluids that infiltrated along the HRSZ. This study provides an important perspective of the interaction of hot granulites with underthrusted relatively cold greenschist‐facies rocks along the steeply north‐dipping section of the HRSZ, and shows that evidence for such interaction is restricted to a relatively narrow zone in the footwall of the HRSZ termed a hot‐iron‐zone. The peak mineral assemblage of a garnet‐free amphibolite from the RGB (magnesio‐hornblende + plagioclase + quartz + clinopyroxene + titanite + ilmenite) yielded the peak P–T condition of 7–8 kbar and 640–680°C with H2O content of 3.5–3.8 mol%. Clinopyroxene is replaced by actinolite + quartz and epidote + quartz symplectites by a post‐peak hydration event at <5 kbar and <590°C caused by elevated H2O content in the rock (>4.0 mol%), possibly related to fluid infiltration along the HRSZ. Mineral equilibria in a garnet‐bearing amphibolite records a prograde path from 5 to 7 kbar and 540–630°C to the peak conditions at 7.6–8.7 kbar and 620–650°C. A clockwise P–T path suggesting rapid compression and decompression has been inferred for the amphibolites from the RGB, possibly because of pressure increase related to overthrusting of the high‐grade terrane (Southern Marginal Zone of the Limpopo Complex) onto the low‐grade granite‐greenstone terrane, followed by rapid exhumation. The quantity of H2O associated with the amphibolite‐facies metamorphism in the RGB was elevated from the peak stage (M(H2O) = 3.5–3.8 mol%) to the retrograde stage (M(H2O) = 4.0–4.5 mol%) of metamorphism in the RGB, possibly suggesting fluid infiltration not only from internal sources but also from external sources. The results of this study indicate that a H2O‐bearing fluid, which infiltrated along the HRSZ, affected both the footwall and the hanging wall sections of the shear zone, although the effect on the footwall section was limited.