Sept. 26, 2026Updated Sept. 27, 2026, 7:28 a.m. ET<\/p>\n
The Arizona Cardinals<\/a> (1-1) face the San Francisco 49ers<\/a> (2-0) Sunday in Santa Clara, California. Kickoff from Levi’s Stadium is at 4:05 p.m. ET (FOX). Let’s analyze NFL odds around the Cardinals vs. 49ers odds and make our expert NFL picks and predictions<\/a> for the best bets.<\/p>\n The Cardinals, after a 26-14 Week 1 win over the Los Angeles Chargers as 9.5-point road underdogs, were blown out in Week 2 at home 31-7 as 4.5-point underdogs by the Seattle Seahawks , with the Under (40.5) cashing. They managed only 151 total yards of offense and QB Jacoby Brissett passed for only 95 yards on 28 attempts, throwing a touchdown pass and an interception.<\/p>\n The 49ers blew out the Miami Dolphins on Sunday 35-13 as 13.5-point home favorites. QB Brock Purdy earned NFC Offensive Player of the Week honors with 2 TD passes and a rushing touchdown. The defense has allowed 20 points through two games.<\/p>\n The 49ers lead the all-time series against the Cardinals 38-31. They swept the season series last year and have won 6 of the last 8 meetings. They beat the Cardinals 41-22 in Arizona as 3.5-point favorites with the Over (48.5) cashing.<\/p>\n Watch the NFL on Fubo!<\/a>Cardinals at 49ers odds<\/p>\n Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub<\/a> for a full list. Lines last updated Saturday at 7 p.m. ET.<\/p>\n Moneyline (ML): Cardinals +320 (bet $100 to win $320) | 49ers -425 (bet $425 to win $100)Against the spread (ATS): Cardinals +8.5 (-112) | 49ers -8.5 (-105)Over\/Under (O\/U): 48 (O: -108 | U: -110)Cardinals at 49ers key injuries<\/p>\n Cardinals<\/p>\n DL Roy Lopez (groin) questionableCB Max Melton (toe) questionableS Dadrion Taylor-Demerson (back) out<\/p>\n 49ers<\/p>\n DE Nick Bosa (knee, calf) outWR Mike Evans (hip) questionableDE Romello Height (hand) outWR Demarcus Robinson (ankle) outDL James Thompson (ankle) out<\/p>\n USA TODAY Sports Fantasy<\/a>: Sync your ESPN, Yahoo, CBS or Sleeper league in seconds to unlock custom roster advice, expert projections, and start\/sit recommendations built for your team. Stop guessing and start winning. Sync your league now<\/a> !<\/p>\n Cardinals at 49ers picks and predictionsPrediction<\/p>\n 49ers 31, Cardinals 20<\/p>\n The Cardinals have lost 12 of 14 games with Brissett as their starting quarterback. They have lost 7 straight division games. Brissett is 0-5 against division opponents, all losses by at least 17 points.<\/p>\n While Arizona can hang with the 49ers offensively, they do not play well from behind, and the 49ers offense has been tremendous so far.<\/p>\n Purdy is 5-1 in his career against the Cardinals with 12 TD passes and a rushing TD.<\/p>\n Expect the Niners to improve to 3-0, but the spread will give you better value.<\/p>\n PASS.<\/p>\n As noted, the Cardinals’ last 5 games against the NFC West have been losses of at least 17 points, all with Brissett as the starter. Their last 6 losses, dating back to last season, have been ATS losses as well.<\/p>\n The 49ers have won by at least 20 points in both games this season.<\/p>\n BET 49ERS -8 (-118).<\/p>\n The 49ers have scored at least 28 points in both games they have played. The Over has cashed in 6 of these teams’ last 8 meetings.<\/p>\n BET OVER 48 (-108).<\/p>\n Best prop bet<\/p>\n Christian McCaffrey 125+ RUSHING AND RECEIVING YARDS (+180)<\/p>\n He has cleared 125 combined rushing and receiving yards in 3 of the last 4 meetings with the Cardinals, and the other one he just missed it with 121 yards. With multiple receivers hurt this week, the passing game will flow through him.<\/p>\n Betting odds calculator<\/a><\/p>\n For more sports betting picks and tips, check out SportsbookWire.com<\/a> and BetFTW<\/a>. Follow SportsbookWire on X at SportsBookWire<\/a> and on Facebook<\/a>.<\/p>\n Access more NFL coverage:<\/p>\n USA TODAY Sports Fantasy<\/a> | BearsWire<\/a> | BengalsWire<\/a> | BillsWire<\/a> | BroncosWire<\/a> | BrownsWire<\/a> | BucsWire<\/a> | CardsWire<\/a> | ChargersWire<\/a> | ChiefsWire<\/a> | ColtsWire<\/a> | CommandersWire<\/a> | CowboysWire<\/a> | DolphinsWire<\/a> | EaglesWire<\/a> | FalconsWire<\/a> | GiantsWire<\/a> | JaguarsWire<\/a> | JetsWire<\/a> | LionsWire<\/a> | NinersWire<\/a> | PackersWire<\/a> | PanthersWire<\/a> | PatriotsWire<\/a> | RaidersWire<\/a> | RamsWire<\/a> | RavensWire<\/a> | SaintsWire<\/a> | SeahawksWire<\/a> | SteelersWire<\/a> | TexansWire<\/a> |\u00a0TitansWire<\/a> | VikingsWire<\/a> | DraftWire<\/a> | TouchdownWire<\/a> | ListWire<\/a> | High schools<\/a><\/p>\n