There is an increasing interest in using non-wood lignocellulosic materials for the production of wood-based medium density fiberboard (MDF). Agave durangensis Gentry bagasse is a waste product produced in large quantities in the mezcal industry. This study evaluated the incorporation of A. durangensis bagasse fibers (ADBF) to elaborate MDF wood-based panels. Three types of panels with different ratios (wood fibers: bagasse fibers) were investigated. The ratios evaluated were 100:0, 90:10, and 70:30. The density profiles, water absorption, and thickness swell of the panels were determined, as well as the modulus of elasticity (MOE), modulus of rupture (MOR), and internal bond (IB), according to the ASTM D1037-06a standard. The results were compared to the ANSI A208.2-2016 standard. The effect of the addition of ADBF on the properties of the panels was analyzed. Density profiles were comparable among the three types of panels, while water absorption, thickness swelling, MOE, MOR, and IB were similar between panels with ratios of 100:0 and 90:10. Panels with 10% and 30% of ADBF meet the minimum ANSI requirements for quality grade 115. It is feasible to use up to 30% of ADBF in the manufacture of wood-based MDF panels.