Goss’s wilt, caused by the gram-positive bacterium Clavibacter nebraskensis, has become one of the most widely spread corn diseases in the USA and Canada. Considered as a relatively new disease, with limited knowledge about the more recently renamed pathogen causing it is, it is today a serious yield-limiting factor in corn crops in North America. The diversity of C. nebraskensis strains translates into the differential plant responses it causes, ranging from hypersensitive-like response to partial resistance, or otherwise susceptibility expressed as dark, water-soaked spots and shiny patches of dried bacterial ooze on the lesions. Weakly aggressive strains of C. nebraskensis typically appear as the season winds down and the crop is about to be harvested, whereas highly aggressive strains can be found at any point during the growing season. Previous research showed that plant’s ethylene and reactive oxygen species (ROS) are essential in limiting the spread of Goss's wilt symptoms near infection sites by triggering programmed cell death (PCD). Preliminary observations that certain strains induce strong defense responses with very little to no symptoms fed the idea to use them for disease resistance priming. The induction of biosynthetic or responsive genes of ethylene, ROS, and salicylic acid (SA) both at the local and distal tissues is in line with the limited disease symptoms development in response to priming with the weakly aggressive strain before further inoculation with a highly aggressive one. The results further expand our understanding of differential host responses to strains with different levels of aggressiveness. The priming process led to an inhibition of the elongated lesions in the susceptible corn plants in comparison with the unprimed plants. The expression patters of a lectin receptor-like kinase, Salt Intolerance 2 (ZmSIT2), and blue copper binding protein (ZmBCP) suggests them as key mediators of ethylene and ROS homeostasis in corn tissues upon infection. This adds to the pool of knowledge on corn defenses against bacterial pathogens and the mechanism of its biopriming, which could serve as an environment-friendly alternative method to control Goss’s wilt.