Noncentrosymmetry (NCS) is essential for a second-harmonic nonlinear-optical (NLO) crystal; however, the tailored synthesis of NCS materials has historically posed significant challenges because the adjacent dipole moments of constituted NLO-active units in the structure tend to align in opposite directions, resulting in the NLO effect being canceled as in a centrosymmetric (CS) crystal. In this work, we propose a polar-layer-driven strategy, wherein a polarization-layered framework is constructed to constrain the dipole moment to align in the same direction, thereby facilitating the formation of the NCS structure. Taking the layered structure CS K2ZnV2O7 as a prototype compound, a novel vandate K4ZnV5O15Br (KZVB) was rationally synthesized via a multiple sites-oriented cosubstition method. KZVB containing two types of NLO-active units of V5+ d0 and Zn2+ d10 cations can be utilized as a mid-infrared NLO crystal with a remarkable NLO response comparable to that of nonoxide AgGaS2. This work not only broadens the effective strategy for designing novel NCS compounds but also provides a progressive development of NLO materials.