Spain could have become the first team to qualify for a place in the four-team finals next summer had they won in Seville.
But a young England side raced into a three-goal lead by half-time and then survived a second-half onslaught for a shock 3-2 win, their first in Spain since 1987.
Raheem Sterling fired England into a 16th-minute lead when he latched onto a well-weighted pass from Marcus Rashford and lashed a powerful drive past David De Gea.
It was a confident strike from the Manchester City winger for a first goal for his country in more than three years.
Rashford, guilty of two poor misses in Friday’s goalless draw in Croatia, made amends after half an hour with a classy second after he was put through by Harry Kane.
Rashford ➡️ Sterling ⚽️
— VERSUS (@vsrsus) October 15, 2018
Raheem with an absolute boss finish to notch his first away goal for England. Finish. pic.twitter.com/p84mGwJfwQ
With Spain reeling Sterling made it three, Kane turning Ross Barkley’s lob across the six-yard box to give the 23-year-old a tap-in seven minutes before half-time.
Paco Alcacer pulled one back with a header after the break, and Spain were adamant they should have had a penalty when England goalkeeper Jordan Pickford appeared to tug at the shirt of Rodrigo.
Sergio Ramos headed a second for Spain deep into stoppage time but it was too late as England registered their first win in the new international tournament.
Two goals from Edin Dzeko gave Bosnia and Herzegovina a 2-0 win over Northern Ireland.
The Roma striker opened the scoring in the 27th minute after a mistake by Jamal Lewis.
And in the 72nd minute Dzeko curled a delightful right-footed finish into the far corner to seal three points for the hosts.
Second-half goals from Haris Seferovic and Michael Lang helped Switzerland to a 2-1 win in Iceland, Adam
Szalai scored twice as Hungary drew 3-3 in Estonia, and Pyry Soiri and Glen Kamara were on target in a 2-0 win for Finland over Greece.
Elsewhere Luxembourg beat San Marino 3-0 and Belarus and Moldova drew 0-0.
