Hart, who has been England's first choice goalkeeper for the last three major tournaments, was backed by Southgate after being deemed surplus to requirements by Pep Guardiola at City as the 31-year-old remained first choice during England's unbeaten qualifying campaign.
Hart's omission means the experienced trio of Jordan Pickford, Jack Butland and the uncapped Nick Pope will be Southgate's options between the sticks.
Pickford has also yet to feature in a competitive international, whilst Butland's only two competitive starts came in qualifying dead rubbers against Lithuania in 2015 and 2017.
Jack Wilshere is also set to miss out despite an impressive end to the season with Arsenal.
Wilshere was initially included in Southgate's squad for March's friendlies against the Netherlands and Italy, but was forced to pull out with a knee injury that cost him the opportunity to make his case.
In defence, Phil Jones's return to form and fitness for Manchester United could see him see off club team-mate Chris Smalling and Chelsea captain Gary Cahill for a place alongside Southgate's preferred centre-back duo of John Stone and Harry Maguire.
- Global stage awaits Kane -
However, at the other end of the field, Southgate is more spoiled for options with Harry Kane and Jamie Vardy both in fine form.
Both failed to carry their club form onto the international stage at Euro 2016, and former England captain Alan Shearer has encouraged Kane to bolster his reputation around the globe by performing on the biggest stage.
"It's a huge tournament for Harry because of what happened two years ago," said Shearer yesterday.
"To put himself on the global stage, he is known all around Europe obviously, but to put himself on a world stage he has to go out and perform and score goals in this tournament."
Another former England great Gary Lineker, who won the World Cup Golden Boot in 1986, believes Kane will relish the responsibility of spearheading England's campaign in Russia.
"There are certain individuals that embrace that pressure and embrace that opportunity to show you can do it on the biggest stage and Harry is that sort of guy," said Lineker.
Southgate has two more warm-up friendlies, against Nigeria on June 2 at Wembley and Costa Rica in Leeds five days later, to fine tune his preparations before England's World Cup begins against Tunisia on June 18.
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