England led 1-0 at the break through a Harry Kane penalty, the captain converting in the 45th minute after Pau Cubarsí had brought him down inside the box. Spain coach Luis de la Fuente responded with a triple change at the start of the second half.
Off went Cubarsí, Fabián Ruiz and Mikel Merino, with Dean Huijsen, Pedri and Fermín López introduced as De la Fuente hunted for control in midfield. His side had struggled to cope with England's pressure in the first half.
The changes brought no calm. England caught the hosts cold with ferocious pressing from the opening minutes of the second half, pushing forward rather than sitting back to protect their lead, and they doubled the score inside four minutes.
Declan Rice swung in a corner in the 53rd minute and Ezri Konsa met it unmarked, heading home to disrupt Spain's plans.
There was no chance to breathe. England were back at the hosts almost instantly, exploiting the space behind the defence on a swift counter. The ball found Jude Bellingham, who slipped it cleverly to the onrushing Ben White, and White finished in the 57th minute for England's third.
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Just as the match looked set for total English control, it sparked back into life in the 63rd minute, 10 minutes after Konsa's goal. Jarell Quansah dallied on the ball, Lamine Yamal pounced and surged into the area, and Elliot Anderson brought him down. The referee pointed to the spot and sent off the Manchester City player.
Mikel Oyarzabal stepped up in the 65th minute and found the net, cutting the deficit to two and reviving Spanish hopes in a fiery encounter on home soil in front of their own fans.
Ten minutes had turned the game on its head. England scored twice in the 53rd and 57th minutes, then Spain hit back through Oyarzabal's penalty after Anderson's 63rd-minute dismissal, setting the remaining minutes alight as the hosts chased their way back in.
The drama kept coming. Fifth substitute Nico Williams grabbed the Matadors' second in the 75th minute, latching onto a swift attack that reached Yamal, whose first-time pass teed up the Athletic Bilbao star to make it a one-goal game.