Joe Gomez and Luke Shaw have been handed starts by England manager Gareth Southgate for the Nations League opener against Spain at Wembley.
Liverpool defender Gomez replaces Kyle Walker on the right-hand side of the back three despite the latter's impressive form on England's run to the 2018 World Cup semi-finals.
Shaw has impressed for Manchester United so far this season and is rewarded with his first cap for 18 months.
Marcus Rashford will support captain Harry Kane – set to receive his World Cup Golden Boot kick-off – in attack, with Manchester City's Raheem Sterling ruled out due to a back injury.
David de Gea starts in goal for Spain in Luis Enrique's first game at the helm, despite some pre-match clamour for Chelsea's Kepa Arrizabalaga to get the nod between the posts.
Sergio Ramos will be partnered by Real Madrid colleague Nacho at centre-back following Gerard Pique's international retirement, while the creative burden in midfield rests with Thiago, Saul Niguez and Isco after cap centurions David Silva and Andres Iniesta stepped away.
Overall there are six changes from the side that was dispiritingly knocked out of the World Cup on penalties by hosts Russia in the last 16.
Iago Aspas missed the decisive penalty in that Moscow shoot-out but starts, despite only being called up by Luis Enrique as a late replacement for Diego Costa.