The WRKY web, which is comprised of a subset of WRKY transcription factors (TFs), plays a crucial role in the regulation of plant immunity, however, the mode of organization and operation of this network remains obscure, especially in non-model plants such as pepper (). Herein, , a member of a subgroup of IIe WRKY proteins from pepper, was functionally characterized in pepper immunity against . CaWRKY22 was found to target the nuclei, and its transcript level was significantly upregulated by inoculation (RSI) and exogenously applied salicylic acid (SA), Methyl jasmonate (MeJA), or ethephon (ETH). Loss-of-function , caused by virus-induced gene silencing (VIGS), enhanced pepper’s susceptibility to RSI. In addition, the silencing of perturbed the hypersensitive response (HR)-like cell death elicited by RSI and downregulated defense-related genes including , , , , , , and . CaWRKY22 was found to directly bind to the promoters of , , and by chromatin immuno-precipitation (ChIP) analysis. Contrastingly, transient overexpression of in pepper leaves triggered significant HR-like cell death and upregulated the tested immunity associated maker genes. Moreover, the transient overexpression of upregulated the expression of and while it downregulated of the expression of . Conversely, the transient overexpression of , , and upregulated the expression of , while transient overexpression of downregulated the transcript levels of . These data collectively recommend the role of CaWRKY22 as a positive regulator of pepper immunity against , which is regulated by signaling synergistically mediated by SA, jasmonic acid (JA), and ethylene (ET), integrating into WRKY networks with WRKY TFs including CaWRKY6, CaWRKY27, CaWRKY40, and CaWRKY58.