Scotland claimed a first win at Twickenham since 1983 as returning fly-half Finn Russell orchestrated a shock 11-6 Six Nations victory over England.
Capitalising on the hosts' ill discipline, Russell gave Scotland a three-point lead before helping to set up Duhan van der Merwe's try.
Defending champions England clawed back six points and Russell's charge was briefly halted by a yellow card.
But a resilient Scotland were undeterred and added another penalty.
England had been favourites to win the tournament but, with France having opened their Six Nations with a 50-10 defeat of Italy, their chances suddenly seem much slimmer.
Scotland, on the other hand, look likely to improve on last year's fourth-place finish with Wales their opponents at Murrayfield next weekend.
That is one of three home games for the Scots in the 2021 Six Nations, with round three's trip to Paris now looking decisive for their title hopes.
Scotland bear burden of Twickenham history
There was no shortage of history surrounding the Calcutta Cup match. It marked the 150th anniversary of the first time England and Scotland played each other and the fact Scotland were without a win at Twickenham in 38 years was a key talking point in the build-up.
All the players had been confined to coronavirus bubbles in the week before the tournament, with England only allowed to socialise outside or otherwise stay alone in their rooms.
The joy of breaking free of their confines combined with the sense of occasion meant both sides sprung out onto the Twickenham pitch, but it was Scotland who looked keenest, determined to throw off the shackles of such a long winless run south of the border.
England, who fielded a relatively inexperienced front row with three experienced props absent, proceeded to concede four penalties in the first five minutes.
The fourth gave Russell - who was returning to international duty after a shoulder injury - the chance to put Scotland ahead.
England's lack of attacking prowess drew criticism in their victorious Autumn Nations Cup campaign and they had promised better in 2021, but it was the visitors who shone in that area as debutant Cameron Redpath made repeated breaks.
For the hosts, the misdemeanours continued. On the eighth penalty conceded, referee Brace had had enough and sent number eight Billy Vunipola to the sin-bin after catching him offside.
As England's penalty count entered double digits, the visitors got their just reward.
It started with Russell and travelled through a who's who of Scotland's backline, the excellent Stuart Hogg, Redpath and hooker George Turner combining to feed Van der Merwe, who stepped inside and powered over near the left corner.
The celebrations were briefly halted as Scotland gave away a penalty and England captain Owen Farrell sent the ball over from just inside his own half.
As Farrell lined up a second penalty, he suggested the television match official reviewed a trip by Russell on England scrum-half Ben Youngs - leading to a yellow card for the talismanic 10.
After Russell had left the field, Farrell scored his penalty and cut Scotland's lead to two.
Scotland keep up unrelenting pressure
Less optimistic Scotland fans might have thought their side would unravel with Russell off the pitch but, after gathering their thoughts at half-time, the visitors continued to look threatening without their main man.
Some had said that at an empty Twickenham and with several England leaders missing, this was Scotland's best chance of a win since 1983.
England boss Eddie Jones questioned before the match whether that expectation might become "heavy" for the Scots, but they looked to be carrying their lead lightly as the second half wore on.
In the absence of Russell, Hogg stepped up to show he had his own box of tricks. A sublime kick to the corner meant Van der Merwe came close to another try and, although Scotland did not get five points, they were rewarded with the return of their fly-half.
Not only were Scotland outplaying England in attack, they were outgunning them at their own kicking game with Hogg continuing to make good use of his boot.
England's defence managed to avoid further embarrassment by halting a Scotland maul a few metres out and Redpath continued to show his quality.
The centre - son of former Scotland captain Bryan - surely caught the eye of British and Irish Lions coach Warren Gatland in the stands as he stole the ball from Tom Curry on the floor, much to the delight of the Scottish bench.
The Scots did not let up and if anything their pace only became more relentless as the end drew near. Jonny Gray lifted England wing Jonny May off the ground to win a maul, Russell tried for one more drop-goal, but it was not to be.
The final whistle blew and it could almost have been a Scotland home game. All that could be heard at Twickenham were the cheers of every single member of the travelling Scottish side.
Man of the match: Finn Russell
'There's a lot more to come'- what they said
England head coach Eddie Jones told BBC Radio 5 Live: "They played tough, edged the set-piece, won in the air and we just could not get in the game. We were not at the races today.
"I take responsibility - I didn't prepare the team well enough. We just had one of those days. We don't have many, but we had a bad day today."
Scotland head coach Gregor Townsend told BBC Radio 5 Live: "There was a calmness on and off the field. I don't know whether it's because there's no crowd.
"It felt like the players were in control today. We had a bit of defence to do at the end but the players stood up well. I'm very proud of the performance and there's a lot more to come from the players."
'One of the best Scotland performances ever' - analysis
Former Scotland scrum-half Andy Nicol on BBC Radio 5 Live: "That is one of the best performances Scotland have ever put in.
"There was creativity, physicality, good kicking and an intensity and togetherness - the win was fully deserved.
"That is as dominant a performance from Scotland against England there has been for over 30 years. It was outstanding, an unbelievably good 80-minute performance."
Former England scrum-half Matt Dawson on BBC Radio 5 Live: "What a fabulous tournament we are part of. Not winning for 38 years, then to bring a performance like this. I have never seen a Scotland performance like this. Total dominance in all areas, full stop. Scotland fans should quite rightly be celebrating long into the night."
Line-ups
England: Daly; Watson, Slade, Lawrence, May; Farrell (capt), Youngs; Genge, George, Stuart, Itoje, Hill, Wilson, Curry, B Vunipola.
Replacements: Cowan-Dickie, Obano, Williams, Lawes, Earl, Robson, Ford, Malins.
Sin-bin: B Vunipola (24)
Scotland: Hogg (capt); Maitland, Harris, Redpath, Van der Merwe, Russell, Price; Sutherland, Turner, Z Fagerson, Cummings, J Gray, Ritchie, Watson, M Fagerson.
Replacements: Cherry, Kebble, WP Nel, R Gray, Graham, Steele, Van der Walt, Jones.
Sin-bin: Russell (38)
Referee: Andrew Brace (Ireland)