That led to Cardinals kicker Zane Gonzalez redeeming himself after missing the potential winning field goal earlier in overtime, making a 48-yard kick with 20 seconds left in the extra period to give Arizona a 37-34 win while handing the Seahawks their first loss of the season.
Arizona improved to 5-2, holding on to second place in the NFC West with the 4-2 Los Angeles Rams playing Monday night. Seattle leads the division at 5-1.
Coach Kliff Kingsbury nearly cost the Cardinals the game earlier in overtime when he iced Gonzalez with 2:47 left on second-and-15. Gonzalez made the initial kick but it didn't count, then he missed the next one.
"It was pretty bad, pretty much a complete debacle," Kingsbury said of the series of plays that led up to him icing Gonzalez. "But luckily those guys bailed us out. I got conservative and went for the field goal and then we did not execute our center-left play, get our quarterback blown up and then we were about to get a delay of game and had to take a timeout, kind of freeze our own kicker.
"So, it was about as bad of a coaching job as possible by me. But our guys kept fighting, kept believing and found a way to get it done."
Then came Simmons' pick after a touchdown by Seahawks wide receiver DK Metcalf was nullified by a penalty.
"Couldn't be happier for Isaiah," Kingsbury said. "He's a guy, due to not having an offseason or really a preseason, we've tried to put him in positions to be successful and work him in there but you saw tonight the ability he has to make that play in that situation was huge and will do wonders for him moving forward."
It was just another typical Cardinals-Seahawks game -- full of drama, twists and turns.
Arizona had not beat Seattle at home since 2012. Since then, Arizona had gone 0-6-1 at home against the Seahawks, including the 6-6 tie in 2016, also on a Sunday night. However, Arizona is 5-2 in Seattle during that span.
Then Sunday night happened.
Both teams combined for 1,091 yards -- 572 by Seattle and 519 by Arizona -- the most in a regular season game since 2013.
And Arizona held Seattle, the highest-scoring team in the NFL, to just a touchdown in the second half.
Seemingly, every time the Cardinals came within a score, they couldn't keep the Seahawks from scoring.
When they were down 10-7 in the first quarter, the Seahawks scored twice to go up 20-7.
When they were down 20-14 in the second, the Seahawks scored to go up 27-14.
When the were down 27-24 in the third, the Seahawks scored to go up 34-24, only to see Arizona scored 13 unanswered.
The Cardinals couldn't get to Wilson during regulation but sacked him twice in overtime.
"These are the games you honestly dream about growing up, watching Sunday Night Football, last week playing on Monday," quarterback Kyler Murray said. "These are the games that you want to be a part of and to be a part of these games, you gotta win and you gotta keep winning.
"So, I'm just super proud of the team, the way we fought, not giving up, no matter the circumstances, just keep battling, keep battling. And that's what we did. So, I think that's huge for us to take that next step."
Murray threw for 360 yards, three touchdowns and an interception on 34-for-48 passing. He also had 67 rushing yards and a touchdown on 14 carries.
When the Cardinals needed Murray the most, he came through.
Arizona came within 34-31 with 2:33 left in the game on Christian Kirk's second touchdown of the game, and his fourth in the past two weeks. After forcing Seattle to punt, Murray orchestrated a 54-yard drive in eight plays that took 52 seconds to get the Cardinals into field goal range. He did it through an 11-yard pass to Larry Fitzgerald, a 15-yard run of his own, a 16-yard pass to Kirk and a 12-yard run by running back Chase Edmonds. Then Gonzalez hit a 44-yard field goal as time expired to send the game into overtime.
"I don't think I smiled all game, honestly," Murray said. "Just because it just felt like we just had to have your head down, just keep grinding just because when you're playing Russell, anything's possible, and I think everybody saw it tonight.
"For me, personally, my mindset was just move the ball, do what I do. Move the ball, be myself and lead the guys down the field, make smart decisions, take care of the ball. Whatever I see, go with it, trust it, and do it with conviction and let my guys -- obviously we got a lot of playmakers on my team or on the offense -- get the ball in their hands and let them do what they do."
DeAndre Hopkins had 10 catches for 103 yards and a touchdown. Running back Chase Edmonds, who had two of the biggest plays in overtime, caught all seven of his targets for 87 yards. Larry Fitzgerald had 62 yards while catching all eight of his targets.
The game was moved to Sunday night amid concerns the Buccaneers-Raiders game might have to be postponed because of a positive coronavirus test on the Raiders and additional players being placed on the reserve/COVID-19 list as a result of contact tracing.
The Cardinals head into their bye week before hosting the Miami Dolphins on Nov. 8. Arizona travels to Seattle on Nov. 19, a Thursday night, for their second meeting of the season.
Kingsbury called Sunday night's win "big" because of what it did for Arizona in the NFC West standings. The Cardinals are 2-0 in the division.
"Wanting to be the best, you got to beat the best," Murray said. "And that's just the nature of this game. In any sport, you got to beat the best. So, I think it was a big, big step for us."