The Tremp–Isona basin (south-central Pyrenees, Lleida, Spain) shows maximum development of the Tremp Group (early Maastrichtian to late Paleocene) covering a wide geological record across the Cretaceous–Paleogene (K/Pg) boundary in continental facies. The mineralogy and geochemistry of lutites were used to assess the evolution of weathering from the Maastrichtian to the Eocene, and particularly for the red beds of the Lower Red and Upper Red Units (pre- and post-K/Pg, respectively). Chemical weathering decreased initially in the Maastrichtian (Gray Unit to Lower Red Unit), increasing subsequently from the Paleocene (Upper Red Unit) to Eocene units. ANOVA analysis of mineralogical compositions and cluster hierarchical analysis have been useful tools to select convenient lutites for assessment of weathering evolution by the chemical alteration index and by broadening of the 001 X-ray diffraction line of illite after ethylene glycol solvation. The lesser chemical weathering found in the Upper Red Unit (Danian) is interpreted in the context of relative warming and aridification, in climates of contrasting seasons and pronounced dry seasons.