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Abstract The Karakoram fault (KKF) is an important strike‐slip boundary for accommodating deformation following the India‐Asia collision. However, whether the deformation is confined to the crust or whether it extends into the mantle remains highly debated. Here, we show that the KKF is overwhelmingly dominated by crustal degassing related to a 4He‐ and CO2‐rich fluid reservoir (for example, He contents up to ∼1.0–1.6 vol.%; 3He/4He = 0.027 ± 0.013 RA (1σ, n = 47); CO2/N2 up to 3.7–57.8). Crustal‐scale active deformation driven by strike‐slip faulting could mobilize 4He and CO2 from the fault zone rocks, which subsequently accumulate in the hydrothermal system. The KKF may have limited fluid connections to the mantle, and if any, the accumulated crustal fluids would efficiently dilute the uprising mantle fluids. In both cases, crustal deformation is evidently the first‐order response to strike‐slip faulting.