We investigate the pressure distribution with depth in regions undergoing horizontal shortening and experiencing crustal thickening both analytically and numerically. Our results show that, in a convergent tectonic setting, pressure can be considerably higher than lithostatic (the pressure resulting from the weight of the overburden). Increases in pressure with respect to lithostatic conditions result from both the contribution of horizontal stresses and the flexural vertical loads, the latter generated by the deflection of the upper crust and of the mantle because of the presence of topographic relief and a root, respectively. The contribution of horizontal stresses is particularly relevant to the upper crust and uppermost mantle, where rocks are thought to deform brittlely. In these domains, pressure gradients twice lithostatic can be achieved. The contribution of horizontal stresses is less important in the ductile domains as differential stresses are progressively relaxed; nevertheless, the effects are still noteworthy especially close to the brittle–ductile transition. Flexural vertical loads generated by the deflection of the upper crust and lithospheric mantle are relevant for rocks of the weaker lower crust. As a result of the combination of the two mechanisms, the pressure gradient varies vertically through the lithosphere, ranging from negative (inverted) gradients to gradients up to several times the lithostatic gradient. The pressure values range from one to two times the lithostatic values (1ρgz to 2ρgz).