The crude oil extracted from milk thistle seeds was employed as a precursor for creating biodiesel (BD) via the cosolvent esterification–transesterification process. The high acid value of the extracted oil (11.90 mg KOH/g) encouraged its pre‐esterification in the occurrence of hexane as a cosolvent. The cosolvent esterification of oil diminished its acidity index to below 2.0 mg KOH/g using 1.5:1 hexane:methanol volume ratio, 50°C, 60‐min reaction time, 6:1 methanol:oil molar ratio, and 0.75 wt.% HCl. Alcoholysis reaction of the esterified oil with methanol and a blend of methanol:ethanol to synthesize, respectively, methylic BD and methylic/ethylic BD was accomplished in the presence of hexane as a cosolvent as well. Under the ideal reaction conditions, methylic BD yield and methylic/ethylic BD yield were 96.23% and 95.63%, respectively. The Fourier‐transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) spectra affirmed the lipid transformation from milk thistle seeds into BD. The attained samples of BD exhibited properties conforming to those specified by ASTM D6751. Also, the cosolvent methanolysis kinetic obeyed the pseudo‐first‐order with 35.94 KJ/mol activation energy and 6.32‐s frequency factor.