Rashford was a substitute for Saturday's 0-0 draw at Liverpool but finds himself back in the starting side for Wednesday's clash at the Estadio da Luz.
There are three other changes for Jose Mourinho's side, with Victor Lindelof starting against his former team and Daley Blind and Juan Mata are also back in. Besides Martial, Phil Jones, Ashley Young and Matteo Darmian also miss out from the XI which started at Anfield.
United go into the game with a maximum haul of six points after wins over Basel and CSKA Moscow in their opening two fixtures, but Rui Vitoria's Benfica side are still searching for their first points after defeats to the same two opponents including a 5-0 battering in Switzerland last time out.
Benfica XI: Svilar, Douglas, Ruben Dias, Luisao, Grimaldo, Fejsa, Filipe Augusto, Pizzi, Salvio, Diogo Goncalves, Jimenez.
Subs: Garrido, Mendes, Pinheiro, Pinto, Tavares, Úmaro, Mesaque.
Man Utd XI: De Gea, Valencia, Lindelof, Smalling, Blind, Herrera, Matic, Mata, Mkhitaryan, Rashford, Lukaku.
Subs: Romero, Darmian, Jones, McTominay, Lingard, Young, Martial.