Cu(pz) 2 (ClO 4 ) 2 (with pz denoting pyrazine, C 4 H 4 N 2 ) is among the best realizations of a two-dimensional spin-1 /2 square-lattice antiferromagnet. Below T N = 4.21 K, its weak interlayer couplings induce a 3D magnetic order, strongly influenced by external magnetic fields and/or hydrostatic pressure. Previous work, focusing on the [H, T ] phase diagram, identified a spin-flop transition, resulting in a field-tunable bicritical point. However, the influence of external pressure has not been investigated yet. Here we explore the extended [p, H, T ] phase diagram of Cu(pz) 2 (ClO 4 ) 2 under pressures up to 12 kbar and magnetic fields up to 7.1 T, via magnetometry and 35 Cl nuclear magnetic resonance (NMR) measurements. The application of magnetic fields enhances T X Y , the crossover temperature from the Heisenberg to the X Y model, thus pointing to an enhancement of the effective anisotropy. The applied pressure has an opposite effect [dT N /dp = −0.050(8) K/kbar], as it modifies marginally the interlayer couplings, but likely changes more significantly the orbital reorientation and the square-lattice deformation. This results in a remodeling of the effective Hamiltonian, whereby the field and pressure effects compensate each other. Finally, by comparing the experimental data with numerical simulations we estimate T BKT , the temperature of the Berezinskii-Kosterlitz-Thouless topological transition and argue why it is inaccessible in our case.