In this work, we investigate the contribution of the annihilation process with initial-state radiation to the invisible dark photon (A') searches at the electron fixed-target configurations. For illustration, we consider both the disappearing positron track signature at Belle II and the large missing energy search at NA64. When the dark photon has a narrow decay width, the effect of the initial-state radiation to the annihilation process can dominate over its s-channel and bremsstrahlung counterparts around mA' = 60MeV (mA' = 200MeV) for Belle II (NA64), to enhance the corresponding sensitivity on the kinetic mixing parameter by a factor of up to approximately 2.7 (1.3). For Belle II, we further perform a multi-bin analysis with the spectrum information to better separate the background and signal channels for significant improvement of the sensitivity.