After spending the first nine seasons of his career establishing himself as a defensive force with the Arizona Cardinals, Calais Campbell signed with Jacksonville in the spring of 2017 as a 31-year-old free agent. Expectations were modest for a veteran entering his 10th season, but Campbell blew past every projection, unlocking the absolute peak of his career in teal and black and quickly earning the moniker "Mayor of Sacksonville".

Campbell’s impact was immediate, transformative, and ferocious. Operating as the vocal leader and physical focal point of a terrifying pass rush, he erupted in his very first game with the Jaguars by setting a franchise record with 4.0 sacks against Houston. He finished his inaugural 2017 campaign with a career-high 14.5 sacks, earning First-Team AP All-Pro honors and finishing as the runner-up for AP NFL Defensive Player of the Year. His dominant presence up front powered Jacksonville all the way to the AFC Championship Game, turning a former cellar-dweller into an elite defensive powerhouse.

His three-year run in North Florida was a masterclass in sustained excellence, as he earned Pro Bowl nods in all three seasons with the franchise (2017–2019) along with a First-Team AP All-Pro selection in 2017 and a Second-Team AP All-Pro choice in 2019. Beyond his elite backfield production, Campbell was a revered ambassador for the city and the league off the field, earning the prestigious Walter Payton NFL Man of the Year Award in 2019. His decade of dominance across the league culminated in a selection to the NFL 2010s All-Decade Team.

After three stellar campaigns, Campbell was traded to the Baltimore Ravens in 2020, eventually adding stops with Atlanta and Miami late in his career.

In his relatively brief stay in Jacksonville, Campbell recorded 31.5 sacks, 195 combined tackles (132 solo, 63 assists), 44 tackles for loss, 77 quarterback hits, and six forced fumbles.