Crops emit volatile organic compounds (VOCs) when infested with diseases or pests as a natural self-defense mechanism. These VOCs can effectively indicate the biotic stresses of crops and, hence, can be termed as biomarkers of crop stress. This study reports the development of cupric oxide (CuO) nanoflake-based resistive sensors for the detection of linalool, methyl salicylate, and hexanal, which indicate biotic stresses in multiple crops, including maize. CuO nanoflakes were synthesized using a hydrothermal method. Their lateral dimensions were found to be ∼300 nm, and the thickness was ∼28 nm when studied using a field emission scanning electron microscope. The band gap of the semiconducting material was ascertained to be 1.82 eV through UV–visible spectroscopy. The CuO sensors were tested at different temperatures and were found to exhibit the highest response to all the target vapors at 250 °C. The sensors were tested at different concentrations (25–200 ppm) of the three VOCs. The response of the CuO sensor was found to be the highest for linalool and ranged from 6.7 to 13.3 times. The response was found to be 4.7–12.2 times for methyl salicylate and 1.2–2.7 times for hexanal at 250 °C. As selectivity is an important parameter of any sensor, a novel technique with a simple algorithm considering the response of the CuO nanoflakes at two different temperatures (250 and 300 °C) was developed to improve the selectivity and the prediction accuracy of the sensors.