Additive manufacturing (AM) has significantly advanced in recent years, leading to its adoption in various industries and the development of the three-dimensional (3D) method for carbon-fiber-reinforced thermoplastic (3DP-CFRTP) printing. This process involves reinforcing filaments with continuous carbon fibers to enhance their mechanical properties significantly. However, material defects such as voids and fiber misalignment angles resulting from AM can significantly affect the mechanical properties of 3DP-CFRTP. This study proposes a crucial strategy for predicting the mechanical properties of 3DP-CFRTP, considering material defect effects at micro-, meso-, and macroscales. At the micro-mesoscale, periodic unit cell analysis analyzes the fiber/resin and filament/void structures to obtain elastic moduli and plasticity parameters. The Budiansky–Fleck model is employed to predict the longitudinal compressive strength. At the macroscale, the predicted mechanical properties are applied to analyze the compressive behavior of open-hole laminates. The cohesive zone model is employed to model intra- and interlaminar damage, expressed using the extended finite element method and the interface element. A smeared crack model is employed to model the longitudinal damage for predicting strength. The numerical results are compared with experimental results to validate the proposed method. This method can evaluate the mechanical properties considering material defects and provides valuable insights into the relationship between defects and practical strength.