England face Malta and Slovakia in World Cup qualifiers next month.
Wayne Rooney retired from international duty yesterday after Southgate had told him he wanted him back in the fold.
But Chalobah and Maguire are the new picks int he squad while Jordan Pickford makes up the trio of uncapped players.
“It’s time to look to the future,” Southgate said. “You can see that from the squad we’ve named.”
On Maguire, who joined Leicester from Hull this summer, Southgate said: “I’ve been very impressed. He’s a defender who’s comfortable with the ball.”
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Chalobah has impressed at Watford since joining from Chelsea this summer and Southgate says he and Pickford were the top two players for England’s under 21s this summer.
“It’s well-deserved for his commitment to England,” Southgate said on the 22-year-old
England squad in full
Goalkeepers: Hart, Butland, Pickford, Heaton
Defenders: Bertrand, Cresswell, Cahill, Jones, Maguire, Stones, Keane, Smalling, Walker, Trippier
Midfielders: Dier, Chalobah, Livermore, Henderson, Sterling, Oxlade-Chamberlain, Alli, Lingard
Forwards: Rashford, Welbeck, Kane, Vardy, Sturridge, Defoe