Excitation-evoked calcium influx across cellular membranes is strictly controlled by voltage-gated calcium channels (Ca_V), which possess four distinct voltage-sensing domains (VSDs) that direct the opening of a central pore. The energetic interactions between the VSDs and the pore are critical for tuning the channel’s voltage dependence. The accessory α₂δ-1 subunit is known to facilitate Ca_V1.2 voltage-dependent activation, but the underlying mechanism is unknown. In this study, using voltage clamp fluorometry, we track the activation of the four individual VSDs in a human L-type Ca_V1.2 channel consisting of α_1C and β₃ subunits. We find that, without α₂δ-1, the channel complex displays a right-shifted voltage dependence such that currents mainly develop at nonphysiological membrane potentials because of very weak VSD–pore interactions. The presence of α₂δ-1 facilitates channel activation by increasing the voltage sensitivity (i.e., the effective charge) of VSDs I–III. Moreover, the α₂δ-1 subunit also makes VSDs I–III more efficient at opening the channel by increasing the coupling energy between VSDs II and III and the pore, thus allowing Ca influx within the range of physiological membrane potentials.