Abstract: This study reports the separation of methyl ethyl ketone (MEK), a relevant compound in the biorefinery context, from aqueous solutions using activated carbons derived from avocado seed biomass. Two synthesis routes were explored via chemical and thermal activation with H2SO4 and KOH. A Taguchi experimental design was applied to tailor synthesis conditions, with MEK adsorption capacity as the target property. Adsorption kinetics and isotherms were evaluated to determine the thermodynamic behavior of MEK separation using the best-performing activated carbons. The carbon activated with H2SO4 achieved the highest adsorption capacity (142 mg g−1) at 20 ◦C and pH 4, surpassing KOH-based materials. This enhanced performance correlated to increased surface area and acidic oxygenated functionalities. However, higher pH and temperature reduced the adsorption efficiency for all adsorbents. Comprehensive characterization was performed using XRD, XRF, FTIR, SEM, N2 adsorption–desorption isotherms, pH at point of zero charge, and surface acidity/basicity analysis via Boehm titration. Thermodynamic data and surface  characterization indicated that MEK adsorption occurs via a double-layer mechanism dominated by electrostatic interactions and hydrogen bonding. The findings highlight an optimized approach for tailoring avocado-based activated carbons to efficiently recover MEK from aqueous media, supporting its potential application in downstream purification of fermentation broths for biofuel production and energy transition processes.