Both Callum Wilson and James Maddison are back in the fold after three years out, while a few more regular faces have been left to watch the tournament from home.
Here’s our list of surprises and snubs from today’s announcement...
The Brentford striker earned his first England call-up in September and all roads appeared to be heading towards a ticket to Qatar.
However, Toney failed to get on the pitch against either Italy or Germany and Southgate opted against vast experimentation in the final two games before the World Cup. Toney has since responded with four goals - two of them penalties - in seven games for Brentford, but will have to wait a little longer for his first Three Lions cap.
Winner of the role of 'Harry Kane's back-up'. The Newcastle striker has had bad luck with injuries over the past few seasons, but has six goals in 10 league games this term including a brace against Aston Villa in front of a watching Southgate late last month.
Whether he gets on the pitch is another question - though fresh concerns over Kane's "fatigue" suggest he may be called upon - as he looks to add to the four caps he has already earned, the last coming in 2019.
The People's Choice pick and the player who would have have felt most aggrieved to be staying at home. Maddison has been a shining light in a poor Leicester side this year, scoring 13 and assisting nine in 22 league outings.
There have been concerns over how Maddison would fit in with Southgate's tactical setup, which does not require an out-and-out No10, which Maddison firmly is, but his performances have been too hard to ignore.
The Arsenal defender's World Cup hopes appeared over when he was snubbed for the squad in September, but has shown fantastic versatility at right-back for table-topping Arsenal since.
Can play at back centre-back, in both a two and a three, and at right-back if required. Fully deserves to be included.
The Roma striker has been a regular in recent England squads, having scored 17 Serie A goals last season for Jose Mourinho’s side.
He’s cooled off at the wrong time though, with just three league goals to his name this campaign, and that has coincided with Callum Wilson and Marcus Rashford finding form.
Had the World Cup been in the summer, he would have been a near-certain pick.
He was named in the provisional squad for the Euros last summer but missed out on the final group, and once again he’s just failed to make the cut.
Southgate has opted to gamble on Kalvin Phillips’ fitness instead, despite the Manchester City midfielder not starting a match this season, in a cruel blow to the Southampton captain.
Won Serie A with AC Milan last season and would have fancied his chances of forcing his way into the World Cup squad.
Was sent off early in the home match against Chelsea in the Champions League last month, after also struggling at Stamford Bridge. Would be harsh if those two displays played a decisive role in Southgate's thinking.