Phospholipase Cβ (PLCβ) isoforms, which are under the control of Gαq and Gβγ subunits, generate Ca2+ signals induced by a broad array of extracellular agonists, whereas PLCδ isoforms depend on a rise in cytosolic Ca2+ for their activation. Here we find that PLCβ2 binds strongly to PLCδ1 and inhibits its catalytic activity in vitro and in living cells. In vitro, this PLC complex can be disrupted by increasing concentrations of free Gβγ subunits. Such competition has consequences for signaling, because in HEK293 cells PLCβ2 suppresses elevated basal [Ca2+] and inositol phosphates levels and the sustained agonist-induced elevation of Ca2+ levels caused by PLCδ1. Also, expression of both PLCs results in a synergistic release of [Ca2+] upon stimulation in A10 cells. These results support a model in which PLCβ2 suppresses the basal catalytic activity of PLCδ1, which is relieved by binding of Gβγ subunits to PLCβ2 allowing for amplified calcium signals.