A rapid and sensitive direct immersion solid-phase microextraction (SPME) technique for the analysis of seven chloro (Cl-) and nitro (NO2-) substituted anilines, toluenes, and nitrobenzenes from small volume (1.5 mL) aqueous samples was optimized for gas chromatography using Design of Experiments (DoE). Screening of the SPME factors was performed by a fractional factorial DoE, and the optimization of influential factors was achieved with a central composite multi-response surface DoE. Extraction time, pre-SPME agitation speed, extraction temperature, and desorption temperature were identified as significant factors and their values were set using a desirability function that maximized the extraction of the seven target analytes. Extraction time and agitation speed showed significant interactions for most analytes (α = 0.05). The relative standard deviations (RSDs) for within-day and between-day analyses were below 8%, suggesting that the method was repeatable and reproducible. The obtained limits of detection were in the low µg/L range (1-10) using a Flame Ionization Detector, far below what is needed for industrial contaminated sites (usually >1 mg/L). The optimized SPME method increased the analyte concentration up to 2-3 orders of magnitude compared with direct GC injection. The optimized SPME method was applied to two groundwater samples from a contaminated site in which the concentrations of three of the target analytes were ranged from 0.06 to 9.42 mg/L with RSDs <11%. When the concentrations of the target analytes in the sample matrix were higher than 0.5 mg/L, a competition for the SPME extraction sites was observed where analytes with higher affinity for the fiber material replaced the analytes with lower affinity. As a result, dilution of highly contaminated samples is recommended. This study provided for the first time an analytical method for the quantification of frequently co-occurring contaminants from the chloro­ and nitro- substituted aniline, toluene, and nitrobenzene families.