Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine.