Digital holographic microscopy (DHM) enables the three-dimensional (3D) reconstruction of quantitative phase distributions from a defocused hologram. Traditional computational algorithms follow a sequential approach in which one first reconstructs the complex amplitude distribution and later applies focusing algorithms to provide an in-focus phase map. In this work, we have developed a synergistic computational framework to compensate for the linear tilt introduced in off-axis DHM systems and autofocus the defocused holograms by minimizing a cost function, providing in-focus reconstructed phase images without phase distortions. The proposed computational tool has been validated in defocused holograms of human red blood cells and three-dimensional images of dynamic sperm cells.