The Three Lions come into the clash after a 4-0 victory in Malta on Friday night.
England lead Group F by two points with three games left to play.
And Three Lions boss Gareth Southgate has opted to start United star Rashford, who was a substitute against Malta.
Rashford is partnered by Dele Alli, Alex Oxlade-Chamberlain and Harry Kane in the England attack.
A win for England tonight will take them five points clear at the top of Group F with two games remaining.
Speaking ahead of the game, Southgate said: "We have some exciting players and we want to show that.
"We have a responsibility to get the Wembley crowd on their feet but equally, everywhere we go in the world the home crowd give the team a lift. It will be great if we can get the level of support that stadium can bring.
"The whole country wants to be at the World Cup. It is a great opportunity for us.
"We are playing good opposition so we have to make sure we are tactically prepared, which we will be, but also have belief in the team we have got."
England: Hart; Walker, Cahill, Jones, Bertrand; Henderson, Dier; Alli, Oxlade-Chamberlain, Rashford; Kane.
Subs: Smalling, Butland, Cresswell, Keane, Stones, Chalobah, Livermore, Sturridge, Welbeck, Vardy, Sterling, Heaton.
Slovakia: Dubravka, Pekarik, Skrtel, Durica, Hubocan, Skriniar, Lobotka, Weiss, Hamsik, Mak, Nemec.
Subs: Novota, Gyomber, Gregus, Duda, Mihalik, Rusnak, Hrosovsky, Mazan, Sabo, Kucka, Duris, Polacek.
