The Arizona Cardinals come into their 2025 season opener against the New Orleans Saints carrying an unusual distinction: they are road favorites to begin the year, a rare position for a franchise that has more often played the underdog role, particularly away from home. This speaks volumes about the positive sentiment surrounding the Cardinals, who finished 8–9 in 2024 but managed a stellar 11–6 record against the spread, including 5–1 ATS as road underdogs—a clear sign they consistently exceeded expectations in difficult environments. Head coach Jonathan Gannon has begun to mold the team in his image, blending an aggressive, disciplined defense with a more balanced offensive scheme that looks poised to take a significant step forward in 2025. Quarterback Kyler Murray, fully healthy and entering a critical season in terms of long-term franchise direction, has the tools and supporting cast to re-establish himself as one of the most dynamic signal-callers in the league. His rapport with rookie sensation Marvin Harrison Jr., who was drafted to be the team’s WR1 from day one, will be a key focus in this matchup. Harrison brings elite route-running, body control, and hands that should immediately translate against an aging Saints secondary led by Tyrann Mathieu. The Cardinals’ offensive line, while not elite, has shown improvement with the additions of young interior linemen and increased cohesion through training camp, which should give Murray just enough time to operate in rhythm. On the ground, veteran James Conner remains the workhorse back and continues to provide a bruising presence between the tackles, something that could be vital in neutralizing New Orleans’ aggressive linebacker unit.

Defensively, the Cardinals have an underrated front seven with Zaven Collins and Kyzir White patrolling the middle, while their edge rushers will look to take advantage of a Saints offensive line that has had protection issues and will be starting a young quarterback, either Spencer Rattler or Tyler Shough. Arizona’s strategy will likely focus on early down success, collapsing the pocket, and forcing the Saints’ QB into uncomfortable throwing situations—especially important in a loud dome environment. Special teams remain stable with veteran kicker Matt Prater, whose consistency and long-range capability offer a critical edge in a game projected to be lower-scoring. The betting market has reflected confidence in Arizona, installing them as 4.5-point favorites with a moneyline near –200, a stark contrast from past seasons when they were often long shots early in the year. While the Superdome has historically been a challenging place to win, Arizona’s combination of veteran stability, explosive rookie talent, and a coaching staff that has built strong preparation habits makes them a legitimate threat to control this matchup. If the Cardinals execute their game plan by keeping Murray clean, feeding Harrison early, and pressuring the Saints’ young quarterback into mistakes, they not only have a strong shot at starting 1–0 but also reaffirming themselves as one of the more dangerous “middle-tier” teams in a competitive NFC field.