Abstract The mechanochemical synthesis of zeolites reduces the generation of liquid residues and gaseous pollutants. Herein, MFI zeolites were synthesized by a seed‐assisted mechanochemical pathway. The effect of different synthesis variables, the Na 2 O/SiO 2 and H 2 O/SiO 2 molar ratios and the milling time and speed, and their interactions on physicochemical properties and catalytic performance on alkylation of phenol with tert‐butyl alcohol were studied. Results showed that the Na 2 O/SiO 2 molar ratio may direct the synthesis to the preferential production of MOR instead of MFI. Also, the milling time and speed and their interaction, i. e., (milling time)×(milling speed), impacted the texture of MFI. Meanwhile, the triple interaction, (milling time)×(milling speed)×(H 2 O/SiO 2 molar ratio), changed the concentration of Lewis acid sites. These effects were rationalized by considering that sodium can act as a structure directing agent during the mechanochemical synthesis of MFI while also promoting the incorporation of aluminum to its structure. Meanwhile, milling time and speed were non‐linearly correlated to the milling energy required for forming the aluminosilicate precursor that crystallizes during the hydrothermal stage of the process. Overall, all the mechanochemically synthesized zeolites were less crystalline than both the seed and a sol‐gel synthesized MFI. The catalytic behavior of the mechanochemical MFI was positively correlated with both the density of acid sites and with the concentration of Brønsted sites.