Goss’s wilt and leaf blight is a growing concern for corn growers in Manitoba, Canada. Little is known about the genetic interaction between corn and the bacterial pathogen, Clavibacter nebraskensis (Cn). The objective of this study was to investigate at the molecular level, how corn can defend against Cn. Two lines of corn screened as susceptible (CO447) and tolerant (CO450) to Goss’s wilt and leaf blight, respectively, were inoculated with Cn strains that possess different aggressiveness levels. The highly aggressive Cn strain (CMN14-5-1) produced severe symptoms on CO447, which quickly developed water soaked lesions, and then within a couple days, developed into necrotic lesions. However, symptoms on CO450 exhibited signs of chlorosis, freckling, and necrosis that did not progress, beyond the initial 6 days after inoculation, with the same strains, which were signs of programmed cell death (PCD) within the corn plant. Similar results were observed with the less aggressive Cn strain (DOAB232), though symptoms were less severe. Area under disease progress curve values were estimated for both lesion length and disease severity, which yielded significant differences amongst treatments. Analysis of the expression of 31 genes associated with plant defense was performed on plants challenged with each Cn strain. Four genes, peptidyl-prolyl cis-trans isomerase (PPI), ras-related protein 7 (Rab7), ribosome-inactivating proteins (RIP2), and respiratory burst oxidase homolog protein D (rbohD) were upregulated in CO450 RbohD is one of the genes responsible for reactive oxygen species (ROS) production, a key factor in PCD, so can be considered a defense factor in this study. Four genes, jasmonate-zim-domain protein 20 (jaz20), β subunit ATP synthase (βATP), allene oxide synthase (ZmAOS), and guanosine triphosphate (GTP)-binding protein (RabE1C) were upregulated in CO447. Based on their differential expression in the two corn lines in response to one or the strain, some genes may be suggested as contributors to either susceptibility or tolerance to Goss’s wilt and leaf blight. Along with other findings in Drs. Daayf, Tambong, and Stasolla’s lab, this knowledge can represent a foundation for developing cultivars with higher resistance to Cn.