The Euro 2020 runners-up became the first team to lose back-to-back European Championship finals in the German capital, where La Roja were crowned kings of the continent for an unparalleled fourth time.
There were no goals to be had in a cagey first half, but Spain struck almost straight away in the second period, as 17-year-old Lamine Yamal swept the ball over to the left, where Nico Williams arrived to crash home.
Spain failed to take a few subsequent chances to double their advantage, though, and the Three Lions capitalised on their opponents' wastefulness when Cole Palmer found the bottom corner with an exceptional equaliser.
England's reprieve did not last for long, though, as with 86 minutes on the clock, Mikel Oyarzabal got goal-side of Marc Guehi to meet Marc Cucurella's cross and prod in the title-clinching goal.
Ferdinand: 'England midfield was too open'
The Three Lions only enjoyed 35% of the ball on Sunday evening, as Declan Rice and Kobbie Mainoo struggled to impose themselves on proceedings for the most part alongside Phil Foden and Jude Bellingham.
Spain lost Rodri to injury at half time, but Martin Zubimendi performed admirably in the absence of his stricken teammate, while Fabian Ruiz and Dani Olmo also earned their keep in the middle.
Speaking to BBC Sport after England's crushing defeat, Ferdinand claimed that the battle was won and lost in the centre of the park, slamming the Three Lions' "open" engine room.
"In these games you have to get control of the ball. Tonight the midfield was like a hot knife through butter at times," the former Manchester United man said.
"You can't be so open in these games, you have to be more resolute. It was too easy for Spain to get up the middle and through the pitch."
Gary Neville echoes Ferdinand sentiment
Neville's view was shared by former Red Devils teammate Gary Neville on ITV Sport, who claimed that England were ultimately made to pay for not controlling the game against a team with "quality".
"Spain had a lot of chances, they could have won the game. We got back into it, but we could have been 2-0 down before that and to not control the biggest games has been a problem for England teams in many, many tournaments," Neville said.
"And to have to play from behind the ball and move your whole team up the pitch from the edge of your box to the other end of the pitch is very difficult.
"You can win the odd game doing that, you can win two or three games, but eventually you play a team with too much quality and that is what we found tonight."
Speculation over Southgate's future has been heating up exponentially in the wake of Sunday's loss, and the 53-year-old responded to the uncertainty when asked after the game.