The likes of Ollie Watkins and Sam Johnstone earned their first call-ups to the senior side, while Jude Bellingham has made the cut despite suggestions Borussia Dortmund won't let him travel due to COVID restrictions.
But the biggest shock of all saw Alexander-Arnold dropped altogether, meaning there are no Liverpool players in the Three Lions squad with Jordan Henderson injured.
In Alexander-Arnold's place, the likes of Kieran Trippier, Reece James and Kyle Walker have all been given the nod for the clashes against San Marino, Albania and Poland.
The decision to leave out Alexander-Arnold hasn't gone down well with his club side according to the Athletic, who believe the Three Lions boss has 'never fully trusted' the full-back.
Meanwhile, Drivetime host Adrian Durham, who said it was 'one of England's biggest omissions in many, many years', while Darren Gough believes leaving out Alexander-Arnold 'is like leaving out Harry Kane'.
Jamie O'Hara also had his say on the 22-year-old being left out, saying that it's a sign that Southgate will want to play three at the back.
The England boss stressed this is far from the end for Alexander-Arnold at England but explained he doesn't think the full-back has played as well as he has in recent seasons.
"There are some areas of the pitch where we have some incredible competition for places, and Trent is very unfortunate," said Southgate.
"I don't think he has played at the level that he found in the last couple of years, but I think he is getting very close that now.
"In the last few weeks, he has definitely taken steps in the right direction.
"It's simply that Reece James and Kieran Tripper have had exceptional seasons really with their clubs. Kyle Walker is in great form with Manchester City.
"There are other players in the league who are also playing well in that position, (Matty) Cash at Aston Villa and (Luke) Ayling at Leeds. We have two really good right-backs in the under-21s, so it's a remarkable position of strength.
"What I said to Trent earlier today is I made that same call to Kyle and to Kieran in the past and their response was a good one in the way they took up the challenge and they found themselves back in the squad.
"Trent is of course a super talent and he will I'm certain play a big part for England in the future.
"He misses out this time but we could quite conceivably be sitting here before the summer and he's with us."
Liverpool have been left 'shocked and bemused' following Gareth Southgate's shock decision to omit Trent Alexander-Arnold from his latest England squad for their upcoming World Cup qualifiers.