New structural and tectono-metamorphic data are presented from a geological transect along the Mugu Karnali valley, in Western Nepal (Central Himalaya), where an almost continuous cross-section from the Lesser Himalaya Sequence to the Everest Series through the medium-high-grade Greater Himalayan Sequence (GHS) is exposed. Detailed meso- and micro-structural analyses were carried out along the transect. Pressure (P)–temperature (T) conditions and P–T–deformation paths for samples from different structural units were derived by calculating pseudosections in the MnNKCFMASHT system. Systematic increase of P–T conditions, from ~0.75 GPa to 560 °C up to ≥1.0 GPa–750 °C, has been detected starting from the garnet zone up to the K-feldspar + aluminosilicate zone. Our investigation reveals how these units are characterized by different P–T evolutions and well-developed tectonic boundaries. Integrating our meso- and micro-structural data with those of metamorphism and geochronology, a diachronism in deformation and metamorphism can be highlighted along the transect, where different crustal slices were underthrust, metamorphosed and exhumed at different times. The GHS is not a single tectonic unit, but it is composed of (at least) three different crustal slices, in agreement with a model of in-sequence shearing by accretion of material from the Indian plate, where coeval activity of basal thrusting at the bottom with normal shearing at the top of the GHS is not strictly required for its exhumation.