A chemical cosubstitution strategy was implemented to design potential ultraviolet (UV) and deep-UV nonlinear optical (NLO) materials. Taking the classic β-BaB2O4 as a maternal structure, by simultaneously replacing the Ba2+ and [B3O6]3- units with monovalant (K+), divalent (alkaline earth metal), trivalent (rare-earth metal, Bi3+) ions, and the [B5O10]5- clusters through two different practical routes, 12 new mixed-metal noncentrosymmetric borates K7MIIRE2(B5O10)3 (MII = Ca, Sr, Ba, K/RE0.5; RE = Y, Lu, Gd) as well as K7MIIBi2(B5O10)3 (MII = Pb, Sr) were successfully designed and synthesized as high-quality single crystals. The selected K7CaY2(B5O10)3, K7SrY2(B5O10)3, and K7BaY2(B5O10)3 compounds were subjected to experimental and theoretical characterizations. They all exhibit suitable second-harmonic generation (SHG) responses, as large as that of commercial KH2PO4 (KDP), and also exhibit short UV cutoff edges. These results confirm the feasibility of this chemical cosubstitution strategy to design NLO materials and that the three selected crystals may have potential application as UV NLO materials.