The oldest and most played fixture in international football takes place at a major tournament for just the second time with the Scots aiming to avenge England's 2-0 win at Euro 96.
England manager Gareth Southgate was part of that winning side 25 years ago, but does not want his players to be distracted by the acrimony that surrounds a meeting with Scotland.
"For the fans and for us it is a big occasion but it is another opportunity for three points and our objective is qualification. That is what we have got to focus on," said Southgate.
"I want them to approach it like any other game of football and focus on playing well and (they) don't need to emphasise the other parts too much."
Despite having just 2,500 tickets for the 22,500 crowd limited by coronavirus restrictions, Scottish fans have descended on London in their thousands.
After a 23-year wait to reach a major finals, the Scots were stung by Patrik Schick's double in a 2-0 loss to the Czech Republic on Monday.
Another defeat would leave Steve Clarke's men needing to beat World Cup finalists Croatia heavily in their final game and other results to go their way to have any chance of reaching the knockout stage for the first time.