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Abstract Terrestrial cosmogenic nuclides (TCN) are widely employed to infer denudation rates in mountainous landscapes. The calculation of an inferred denudation rate (D_inf) from TCN concentrations is typically performed under the assumptions that denudation rates were steady during TCN accumulation and that soil chemical weathering negligibly impacted soil mineral abundances. In many landscapes, however, denudation rates were not steady and soil composition was significantly impacted by chemical weathering, which complicates interpretation of TCN concentrations. We present a landscape evolution model that computes transient changes in topography, soil thickness, soil mineralogy, and soil TCN concentrations. We used this model to investigate TCN responses in transient landscapes by imposing idealized perturbations in tectonically (rock uplift rate) and climatically sensitive parameters (soil production efficiency, hillslope transport efficiency, and mineral dissolution rate) on initially steady‐state landscapes. These experiments revealed key insights about TCN responses in transient landscapes. (a) Accounting for soil chemical erosion is necessary to accurately calculateD_inf. (b) Responses ofD_infto tectonic perturbations differ from those to climatic perturbations, suggesting that spatial and temporal patterns inD_infare signatures of perturbation type and magnitude. (c) If soil chemical erosion is accounted for, basin‐averagedD_infinferred from TCN in stream sediment closely tracks actual basin‐averaged denudation rate, showing thatD_infis a reasonable proxy for actual denudation rate, even in many transient landscapes. (d) Response times ofD_infto perturbations increase with hillslope length, implying that response times should be sensitive to the climatic, biological, and lithologic processes that control hillslope length.