Head coach Kliff Kingsbury named Murphy and Tramaine Brock the starting cornerbacks to begin the regular season.
[19] On September 8, 2019, Murphy made his professional regular season debut and earned his first career start, recording five combined tackles (four solo) during a 27–27 tie with the Detroit Lions.
[22] In Week 6, he collected a season-high eight combined tackles (seven solo), two pass deflections, and recovered a fumble during a 38–10 victory at the Dallas Cowboys.
In Week 7 , Murphy recorded two solo tackles and had his first career sack on Russell Wilson as the Cardinals defeated the Seattle Seahawks 37–34 in overtime on Sunday Night Football.
He finished the 2020 NFL season with 51 combined tackles (40 solo), eight pass deflections, two fumble recoveries, and two sacks in 15 games and seven starts.
[26] After starting cornerbacks Patrick Peterson and Dre Kirkpatrick departed in free agency defensive coordinator Vance Joseph was required to fill their roles.
Murphy competed to be a starting cornerback, amongst the likes of Robert Alford, Malcolm Butler, Daryl Worley, Darqueze Dennard, and rookie Marco Wilson.
[27] On September 26, 2021, Murphy made four combined tackles (three solo), two pass deflections, two interceptions, and scored his first career touchdown during a 31–19 victory against the Jacksonville Jaguars.
[29] He finished the 2021 NFL season with a total of 64 combined tackles (49 solo), one touchdown, was credited with half a sack, and lead the Arizona Cardinals with 12 pass deflections and four interceptions in 15 games and 15 starts.
On September 18, 2022, Murphy made one tackle and recovered a fumble by Hunter Renfrow that was caused by Isaiah Simmons for a 69–yard return tos ore the game-winning touchdown during a 29–23 overtime victory against the Las Vegas Raiders.
On December 24, 2022, the Arizona Cardinals placed Murphy on season–ending injured reserve due to a back injury and subsequently lead to him missing the remaining seven games of the season (Weeks 10–18).
On September 24, 2023, Murphy recorded a season-high ten combined tackles (nine solo) and broke up two passes during a 24–28 loss to the Los Angeles Chargers.
Head coach Kevin O'Connell named Murphy a starting cornerback alongside Stephon Gilmore to begin the season.