For the production of biodiesel from waste cooking oil with an acid value of 1.86 mg KOH/g, five heterogeneous catalysts—Ba(OH)₂, CaO, MgO, ZnO, and AlCl₃—were employed. To optimize the reaction parameters of each catalyst, the influence of crucial process variables, such as catalyst loading, methanol-to-oil ratio, and reaction duration, was investigated. In addition, the effect of acetone as a cosolvent toward the progress of biodiesel production and the reusability of the heterogeneous catalysts were also examined, and the data were statistically evaluated with a 95% confidence level. Ba(OH)₂ performed exceptionally well, with a 92 wt.% biodiesel yield, followed by CaO with an 84 wt.% yield. However, none of the results for MgO, ZnO, or AlCl₃ were adequate. In addition, regardless of the type of catalyst utilized, adding 20 vol.% acetone to the biodiesel manufacturing process led to an increase in output. Furthermore, every heterogeneous catalyst was reusable, but only Ba(OH)₂ and CaO produced a significant yield until the third cycle. The other catalysts did not produce yields of any significance.