The objective of this work was to determine the reduction of aflatoxin B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2) as a function of initial moisture content of samples (24%, 27%, and 30%), barrel temperature (140, 170, and 200 ◦C), and residence time (30 to 70 s) when artificially contaminated rice meal was extrusion-cooked. Extruded and unextruded samples were analyzed by high-performance liquid chromatography (HPLC). Extrusion-cooking was observed to reduce aflatoxin (AF) content, which ranged from 51% to 95% depending on the type of AF and the studied variables. Only in the case of AFG2 was it found that the higher the temperature, the higher the moisture content, and the longer the residence time, the greater the reduction. Moisture content had a significant influence on reducing AFB2, AFG1, and AFG2 whereas it was not a significant factor affecting the levels of AFB1. Regardless of the type of AF, the lowest reductions were achieved at a temperature of 140 ◦C. Even though theoretically greater losses would be expected at highest temperature, AFB1 and AFB2 were more reduced by 170 ◦C than by 200 ◦C while AFG1 reductions were not statistically different when processing at 170 ◦C and 200 ◦C. The decrease of AF followed 1st-order kinetics; the fastest treatment in reducing AF was that at 200 ◦C when samples containing AFG2 were wetted to 24% and when samples containing AFB1, AFB2, and AFG1 were hydrated to 27%. By contrast, the slowest treatments were observed at a barrel temperature of 140 ◦C.