In the present study, the preparation of methyl esters of chlorophenoxy acids with trimethylsilyldiazomethane (TMSD) is reported. TMSD is a mild and safe alternative to the highly toxic, thermally labile, and explosive diazomethane. Due to the novelty of this method, the characteristics of the reaction were investigated and the derivatization procedure was screened for statistically significant factors. The parameters identified as influential are the amount of methanol as well as reaction time and temperature. A careful optimization by a complete factorial response surface design was carried out to generate optimal reaction conditions with respect to maximum recovery and reaction yield. Special emphasis has been given to an accurate validation of the derivatization procedure. LODs were determined between 4.1 and 8.1 ng/mL for the enriched sample and linearity was proofed for more than five orders of magnitude. The applicability of the method was demonstrated by the analyses of quality control material including sample preparation with SPE. Polar herbicides investigated in the study belong to acetic acid (2,4-D, MCPA, and 2,4,5-T), butanoic acid (MCPB), and propanoic acid (mecoprop). An efficient, fast, and high-throughput method for the determination of polar herbicides including the potential for automation is proposed.