A hybrid voltage mode (VM) and current mode (CM) four-level pulse amplitude modulation (PAM-4) transmitter circuits (a.k.a. drivers) is calibrated using a configurable replica circuit and calibration control circuitry. The replica circuit includes an on-chip termination impedance to mimic a receiver's termination impedance. The amount of level enhancement provided by the current mode circuitry is calibrated by adjusting the current provided to the output node and sunk from the output node by the replica current mode circuitry while the replica voltage mode circuitry is driving an intermediate PAM-4 level. After the level enhancement has been set, the non-linearity between levels is calibrated by adjusting the amount of current provided to the output node by the replica current mode circuitry while the replica voltage mode circuitry is driving a maximum output voltage level.