The Three Lions host their oldest opposition at Wembley on Friday night having opened their Group D account with victory over Croatia.
While there are 40 places between England and Scotland in the FIFA world rankings, the derby-like feel is likely to somewhat even the odds.
Rashford, who came off the bench during Sunday’s victory, knows how much the fixture means and compared it to some of the biggest club rivalries he has played in.
“I think in football everyone wants to be beat everyone,” he said.
“But in some games… its how the game is actually being played and the atmosphere and crowd and how much you want to win – it all comes together.
“There is something unique about that game. It’s similar to the games against Man City and Liverpool – those type of games you have a different feeling.
“You can’t put a finger on it – because you approach every game the same. But the build up, its just unique and I’m really looking forward to it.
“As players you want to play in the biggest, most historical games. Through our careers this is going to be up there with one of the biggest games that we play, one of the games we rememberfor the rest of our careers.
“For me, I look back at the last time I played against them – the atmosphere, the build up, it was unique. To do it in the Euros is a moment we are looking forward to.”
While there will be rivalry on the pitch from the first whistle, the two nations will come together ahead of kick-off.
Scotland announced last week they would take a knee in solidarity with the England players in a pre-match gesture against racism.
Having initially said they would not take part, Rashford is pleased that Scotland are now on board as it remains to be seen if the stance will again be jeered by a minority of supporters.
Asked if Scotland taking the knee is a symbol of unity, Rashford replied: “Yes, I think it’s an important message.
“We spoke about it in camp and we recognise it is a very important message. If you want to spread important messages then there is no better place to do it than on the biggest stage.
“That is why we continued to take the knee. So them taking the knee is going to be a good thing and if there is more of us spreading the correct message hopefully it has a big influence on people around the world.”
Rashford has not only been taking a knee against racism but also fought the Government in the past year to ensure free school meals for children during the Covid-19 pandemic.
He received an MBE last year for his actions and recently spoke to former United States President Barack Obama.
Obama said Rashford was “way ahead” of where he was as a 23-year-old – but the Manchester United forward ruled out following in his political footsteps.
“Yes, I probably can because it’s not something I grew up wanting to do,” he said when asked if he could rule out ever becoming Prime Minister.
“My mind’s not on that really but it was great speaking to him (Obama) and I’ve enjoyed speaking to people like that, learning from them and taking what I can from the stories that they tell me. It’s something I will always remember.”