Within the framework of the HiLumi-LHC project, CERN is currently manufacturing 11 T dipole and quadrupole accelerator magnets using state-of-the-art Nb3Sn Rutherford cables. Even higher magnetic fields are considered by the Hadron Future Circular Collider (FCC-hh) design study, which plans to develop 16 T Nb3Sn bending dipoles. In such high-field magnets, the design pre-stress can reach considerable values (150–200 MPa) and, since Nb3Sn is a brittle compound, this can constitute a technological difficult challenge. Due to the significant impact that a transverse load can have on the performances of a Nb3Sn magnet, CERN has launched a campaign of critical current measurements of reacted and impregnated Nb3Sn cables subjected to transverse pressure up to about 210 MPa. In this paper, results obtained on 18-strand 10-mm-wide cable sample based on a 1-mm-diameter powder-in-tube (PIT) wire are presented. The tests were carried out on a 2-m-long sample by using the FReSCa test station, at T = 4.3 K and background magnetic fields up to 9.6 T. For applied pressures below ≈ 130 MPa, only reversible reductions of the critical current, Ic, are observed. At higher pressures, a permanent Ic reduction occurs; such irreversible behaviour is due to the residual stresses generated by the plastic deformations of the copper stabilizer. This type of current reduction, whether reversible or not, is fully governed by the strain-induced variations of the upper critical field, Bc2. At higher pressures, estimated between 180 and 210 MPa, it is indeed plausible to believe that cracking of filaments occurs, with detrimental consequences for the Nb3Sn cable’s electrical performances. The complete set of critical current data here presented, collected at different pressures and as a function of the applied magnetic field, allows for the first time to investigate the evolution of superconducting parameters such as the upper critical field Bc2 in the irreversibility region, where both the effects of Cu matrix plasticization and/or cracking of filaments may occur. The experimental approach and data interpretation have a general value and can be applied to any typology of Rutherford cable.