Chemiresistive vapor sensors combining functionalized gold nanoparticles and single-stranded DNA oligomers are investigated to enhance specificity in chemical sensing. Sensors are made by depositing DNA-functionalized gold nanoparticles onto microfabricated electrodes using four distinct sequences. Sensor performance is evaluated for response to relative humidity and exposure to vapor analytes including ethanol, methanol, hexane, dimethyl methylphosphonate, and toluene under different relative humidity. It is found that sensors display a nonmonotonic resistance change toward increasing humidity due to the combined effects of hydration induced swelling and ionic conduction. Responses to vapor analytes show sequence-dependent patterns as well as a strong influence of humidity. Overall, the findings are encouraging for using DNA oligomers to enhance specificity in chemical sensing.