England's players will not have enough time to adapt to the challenges of playing at high altitude before they take on Mexico, says Tuchel.
Harry Kane's double against DR Congo booked England's trip to Mexico City's Azteca Stadium - which is around 7,200ft above sea level.
At that altitude, the Earth's barometric pressure is lower, making the air thinner and meaning less oxygen is taken into the bloodstream with each breath, which creates clear difficulties for athletes and is likely to become a key factor in the game for England.
Mexico, meanwhile, have played all four of their World Cup games at high altitude, with three matches at the Azteca Stadium and the other in Guadalajara – which is around 5,000ft above sea level - so their players are accustomed to the thinner air.
"The altitude will be a big disadvantage because we cannot physically adapt to it," said Tuchel.
"It just takes too much time. We have only three days in between these matches. It's physically just not possible to adapt to the altitude."
Research suggests athletes competing at high altitude should spend a week or two living at that level in order to allow their body to acclimatise and generate more red blood cells.
But England will only be arriving in Mexico City two days before the match.
"That is just a huge advantage that Mexico will have," added Tuchel.
"More obstacles may come, but we are ready for that.
"This is just something with which we will have to deal. And I think we showed the attitude that we are ready for that."