This research presents two hybrid models based on the Streter-Phelps equation associated with nonstationary conditions dS/dt≠0 and advective dS/dZ≠0, statistically adjusted and applicable for the design of anaerobic upflow filters separated in two and three phases, operated on a laboratory scale using landfill leachate as substrate under a 33 experimental factorial design. The factors included (1) volumetric organic load (VOL)=2.25, 3.45, and 4.64 kg CODm−3day−1 [chemical oxygen demand (COD)]; (2) temperature (T)=20°C, 27°C, and 34°C; and (3) height ratios (D1 = height phase 1, D2 = height phase 2, and D3 = height phase); DI-FAFS (Spanish acronym that means Upflow Anaerobic Filter separated in Two Phases): D1/D2=20%/80%, 50%/50%, and 80%/20%, and TRI-FAFS (upflow anaerobic filter separated in three phases): D1/D2/D3=4%/16%/80%, 10%/10%/80%, and 16%/4%/80%. Operating conditions included (1) hydraulic retention time (HRT) between 16 and 18 h; (2) flow rates of 3.5–4.0 mL min−1; (3) surface hydraulic load of 1.82 m3 m−2 day−1; and (4) filter total depth of 1.2 m, filled with plastic material with a specific surface area of 476.35 m2m−3. Fifty-four tests were performed, obtaining efficiency between 27% and 73% in the DI-FAFS and between 84% and 94% in the TRI-FAFS (Spanish acronym that means Upflow Anaerobic Filter separated in Three Phases). Maximum efficiencies were achieved with D1/D2 ratios 20%/80% and D1/D2/D3=10%/10%/80%, respectively, with temperatures ≥27°C and VOL≥3.45 kgCODm−3day−1.