Even with Leeds United's Patrick Bamford and Sheffield-born Dominic Calvert-Lewin amongst a number of players missing through injury, Southgate has resisted the temptation to select Greenwood. Ollie Watkins is prefered.
Yorkshiremen Kalvin Phillips, John Stones and Kyle Walker, mainstays of the squad, are selected as expected but Harry Maguire is another to miss out through injury, as does Liverpool's Trent Alxander-Arnold.
Now 23, Tomori made 26 appearances on loan at Hull from Chelsea in the 2017-18. He is one of many talented young players who has had to kick-start his career, moving on loan to AC Milan at the end of last season and making the switch permanent in the summer.
His form in Serie A has been rewarded with an England call-up, with former Leeds loanee Ben White - now at Arsenal - overlooked.
Tomori's only previous international appearance came as an 84th-minute substitute in Kosovo in 2019.
There is no place for Chelsea's Ben Chilwell, struggling to play regular club football ahead of Marcos Alonso this season.
Greenwood has not played since he was sent home from England duty at the start of last season for breaking Covid-19 protocols when he and Phil Foden invited girls back to their hotel room. Southgate, who quickly recalled Foden, says he is trying to time Manchester United forward Greenwood's return correctly in view of his long-term development.
England play World Cup qualifiers away to Andorra and at home to Hungary.
Goalkeepers: Jordan Pickford, Aaron Ramsdale, Sam Johnstone
Defenders: Kyle Walker, Reece James, John Stones, Tyrone Mings, Conor Coady, Fikayo Tomori, Luke Shaw, Kieran Trippier
Midfielders: Declan Rice, Kalvin Phillips, Jordan Henderson, Mason Mount, Jesse Lingard
Forwards: Jack Grealish, Phil Foden, Raheem Sterling, Jadon Sancho, Bukayo Saka, Harry Kane, Ollie Watkins.