This work describes the optimization and validation of an analytical method for the quantification of short- and medium-chained chlorinated paraffins (SCCPs and MCCPs, respectively) in a range of food matrices using gas chromatography-electron capture negative ionization-mass spectrometry (GC-ECNI/MS). A dispersive solid phase extraction (dSPE) method was optimized for fish, meat, oil, milk and whole-grain cereal followed by clean-up with concentrated sulfuric acid and acid silica. Fractionation using silica cartridges efficiently removed a number of potentially interfering halogenated compound classes from sample extracts while retaining 96% of ∑SCCPs and 99% of ∑MCCPs. Limits of quantification (LOQs) estimated for food samples ranged from 0.7 to 6.0 ng/g wet weight (ww) for ∑SCCPs and 1.3–12 ng/g ww for ∑MCCPs. The applicability of the optimized protocol was assessed in each of the described food matrices via repeated analysis (n = 3) of samples fortified with SCCP 55.5%Cl and MCCP 57%Cl technical mixtures at two concentration levels and spiked lard samples from a recent European Union Reference Laboratory (EURL) interlaboratory study on CPs in food. The EURL's accuracy criteria was met for both homologue groups in all food matrices with overall accuracy in the range of 76–130% for in-house spiked samples and 57–150% for the EURL lard analysis. Excellent precision was observed for most samples with relative standard deviation (RSD) between replicates (n = 3) ≤ 12% for ∑SCCPs and ≤17% for ∑MCCPs in all food matrices analysed. The selection of the internal standard was a significant factor in the accuracy of the method and highlights the strong need for more appropriate isotopically labelled CP standards.