Gareth Southgate's four-game spell in charge of England ended in late disappointment as Spain came from two behind to deny the hosts victory in a thrilling 2-2 draw at Wembley.
A penalty from Adam Lallana gave the hosts the lead inside the opening eight minutes of the contest with a superb diving header from Jamie Vardy two minutes into the second half doubling their lead.
While England looked comfortable, former Liverpool misfit Iago Aspas pulled one back for the visitors with a superb late strike in the final minutes of normal time before Real Madrid midfielder Isco found an equaliser in injury time.
There was a further blemish on the evening for England, with Adam Lallana forced off during the first-half following a late challenge from Thiago Alcantara, leaving Liverpool and Jurgen Klopp with an anxious wait to learn the severity of the injury.
After dispatching Gordon Strachan's Scotland in efficient fashion on Friday, England denied Spain room to breathe in a vibrant start to Southgate's final game in charge as interim manager. Their breakthrough came after just eight minutes but was proceeded by the night's controversial moment with a lunge from Vardy leaving Chelsea's Cesar Azpilicueta in agony just inside his own half.
The Leicester City striker, while quick to close down the full-back, was late and high on his opponent with his follow up challenge. While a card should have emerged, it was Vardy who prompted England's opener. Lallana's sublime ball in from the right deceived Inigo Martinez, slipping through to Vardy whose initial first touch let him down. His presence inside the six yard area was enough to prompt Pepe Reina to come rushing out, however, with the Napoli goalkeeper taking out the England striker in what was his first appearance for La Roja since 2014.
Lallana made no mistake from the penalty spot but soon after his evening was brought to an end. Having wriggled free from Thiago out on the touchline, the Bayern Munich midfielder felled his opponent with another desperately poor challenge that forced the Liverpool playmaker to head off straight down the tunnel, with Theo Walcott replacing him.
While it was Lallana who started as the bright spark for the home side, Raheem Sterling soon took up that responsibility following his teammate's departure, tormenting Dani Carvajal and combining neatly with Jesse Lingard to create the space in behind the Spanish defence with ease.
Spain's best chance of the half fell to another debutant in Vitolo, who found himself well placed on the edge of the box after neat build up from Juan Mata and Thiago, only to drag his shot harmlessly wide of Joe Hart's goal.
England had done away with the attempts to persistently play the ball out from the back we saw against Scotland and instead focused on applying pressure on the opposition at every opportunity. That approach paid off throughout the first-half and continued to do so early in the second.
The home fans did not have to wait much longer to celebrate again, with Vardy creeping in from the left to pounce on a terrific whipped cross from captain for the night Jordan Henderson with a superb diving header hammered past Reina, scoring his first goal in 937 minutes of football for club and country.
A suicidal pass across his own goal from Martinez left England racing forward for a third just minutes later, with Vardy instead choosing to thread through Walcott. His effort was well saved by Reina, however.
That flurry finally woke up Spain, who worked the England goalkeeper for the first time on the hour, but Tom Heaton, who had replaced Joe Hart at half-time, was alive to make an instinctive block to deny Aspas.
With both sides ringing in changes as the second half progressed, Manchester United's Ander Herrera was introduced off the bench to help try spark his side into life, with Alvaro Morata also entering the fray.
On an evening where Spain struggled to produce anything of real quality, Aspas reignited his side's hopes, cutting in from the left and curling a superb strike around Heaton and into the top corner. Isco, having been introduced with his side trailing, sealed an unlikely comeback with a precise finish.