Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) is the first line of defense in plant disease resistance. However, the molecular mechanisms of plant PTI vary across species, making it challenging to identify a core set of trait-associated genes. This study aimed to investigate key factors that influence PTI and identify the core molecular network in Sorghum bicolor, a C4 plant. We performed comprehensive weighted gene co-expression network analysis and temporal expression analysis of large-scale transcriptome data from various sorghum cultivars under different PAMP treatments. Our results revealed that the type of PAMP had a stronger influence on the PTI network than did the sorghum cultivar. Following PAMP treatment, 30 genes with stable downregulated expression and 158 genes with stable upregulated expression were identified, including genes encoding potential pattern recognition receptors whose expression was upregulated within 1 h of treatment. PAMP treatment altered the expression of resistance-related, signaling, salt-sensitive, heavy metal-related, and transporter genes. These findings provide novel insights into the core genes involved in plant PTI and are expected to facilitate the identification and application of resistance genes in plant breeding studies.