Campylobacter jejuni is a leading cause of food-borne gastroenteritis in humans. It lives commensally in the gastrointestinal tract of animals, and tolerates variable conditions during transit/colonization of susceptible hosts. The C. jejuniCprRS two-component system contains an essential response regulator (CprR), and deletion of the cprS sensor kinase enhances biofilms. We sought to identify CprRS-regulated genes and better understand how the system affects survival. Expression from the cprR promoter was highest during logarithmic growth and dependent on CprS. CprRD52A did not support viability, indicating that CprR phosphorylation is essential despite the dispensability of CprS. We identified a GTAAAC consensus bound by the CprR C-terminus; the Asp52 residue of full-length CprR was required for binding, suggesting phosphorylation is required. Transcripts differing in expression in Delta cprS compared with wildtype (WT) contained a putative CprR binding site upstream of their promoter region and encoded htrA (periplasmic protease upstream of cprRS) and peb4 (SurA-like chaperone). Consistent with direct regulation, the CprR consensus in the htrA promoter was bound by CprRCTD. Finally, Delta htrA formed enhanced biofilms, and Delta cprS biofilms were suppressed by Mg2+. CprRS is the first C. jejuni regulatory system shown to control genes related to the cell envelope, the first line of interaction between pathogen and changing environments. Campylobacter jejuni is a leading cause of food-borne illness, and understanding how it adapts to different environments is key to infection control. Here, we characterize the activity, regulation, and regulon of the conserved C. jejuni two-component regulatory system, CprRS. We find that response regulator phosphorylation, like the regulator itself, is essential for viability, and that the system regulates processes and genes related to the cell envelope, including the htrA periplasmic serine protease.