Ca2+is an important signaling messenger. In microorganisms, fungi, and plants, H+/Ca2+antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca2+by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca2+in two distinct modes: a low-flux H+/Ca2+exchange mode and a high-flux mode in which Ca2+and phosphate ions are co-transported (1:1) in exchange for H+. Coupling with phosphate greatly accelerates the Ca2+efflux activity of YfkE. Our studies reveal that Ca2+and phosphate bind to adjacent sites in a central translocation pathway and lead to mechanistic insights that explain how this CAX alters its conserved alpha-repeat motifs to adopt phosphate as a specific “transport chaperon” for Ca2+translocation. This finding uncovers a co-transport mechanism within the CAX family that indicates this class of proteins contributes to the cellular homeostasis of both Ca2+and phosphate.