Fikayo Tomori has been handed an England recall by Gareth Southgate after Harry Maguire was ruled out through injury.
Ollie Watkins is back in the squad in place of Patrick Bamford, who made his international debut last month.
Luke Shaw, Reece James and Mason Mount have all been picked for the squad despite fitness concerns in recent days.
England are set for two World Cup qualifiers away to Andorra on October 9 and at home to Hungary three days later.
United captain Maguire has a calf injury and went off midway through the second-half in their 1-0 defeat to Aston Villa last Saturday. His manager Ole Gunnar Solskjaer says he will be out for ‘a few weeks’.
Right-back Alexander-Arnold has a groin injury and didn’t travel with Liverpool to Porto for their Champions League match in midweek.
Chelsea wing-back James has an ankle injury and limped off during their 1-0 defeat to Manchester City last weekend but is included for the international double-header.
Southgate had said prior to the squad announcement he would ease Liverpool centre-back Joe Gomez back into the international scene after he returned to action following 10 months out with a serious knee injury.
Maguire’s absence compounds Southgate’s central defensive issues with John Stones, another first choice, yet to play a single minute for Manchester City this season.
But Stones does make the squad and could partner Tomori, Conor Coady or Tyrone Mings.
On Fikayo Tomori, who has started the season impressively at AC Milan, Southgate said:
‘He’s playing at a club where there’s an expectation to win every week, so he’s performing under pressure.
‘I like Fikayo Tomori in terms of his aggressiveness as a defender. Because he’s got speed he’s confident enough to defend on the front foot and his use of the ball is improving all the time.’
Leeds United forward Bamford was given a chance to impress in last month’s World Cup qualifiers against Hungary, Andorra and Poland but doesn’t make it this time with Watkins coming back in.
Southgate said: ‘We would have selected Ollie last month but he was injured. He was very close to making the squad for the Euros.
‘I loved his mentality when he was working with us. He didn’t come in, have a look at things and dip a toe in the water, he was really determined to take the opportunity.
‘We have got some good centre forward options, a couple missing with injury, but Ollie impressed us with his mentality and his ability when with us.’
Arsenal goalkeeper Aaron Ramsdale gets a call-up and Manchester City’s Phil Foden is back in after missing last month’s games through injury.
There’s no Jude Bellingham either despite a good start to the season with Borussia Dortmund but Chelsea’s Mason Mount is in despite recent injury issues.
On the omission of Bellingham and also Man United’s Mason Greenwood, Southgate said: ‘They are young players with a heavy load at the moment. Jude is playing Champions League games, he’s playing league games, as an 18-year-old he had a full season last season and then into a European Championship with no break.
‘We have to remember these lads are still physically growing so when we’re talking about young player development we have to be careful in how we handle them.
‘These are two players we think can be exciting players for England in the future but we don’t want to overload them.’
England are in control of Group I with four matches left to play. They lead Albania by four points and are five ahead of Poland. Southgate’s men need eight points from their remaining four games to be assured of a place in Qatar.