Sancho, 18, has assisted in five league goals for Dortmund this season as he has helped them top the Bundesliga after six games.
Reports suggested he would be handed his first U21 call but an impressive performance and an assist against Monaco on Wednesday changed Southgate's mind.
England squad: Bettinelli (Fulham), Butland (Stoke City), McCarthy (Southampton), Pickford (Everton); (Liverpool), Gomez (Liverpool), Maguire (Leicester), Rose (Tottenham), Shaw (Man Utd), Stones (Man City), Tarkowski (Burnley), Trippier (Tottenham), Walker (Man City); Barkley (Chelsea), Chalobah (Watford), Dier (Tottenham), Henderson (Liverpool), Mount (Chelsea), Winks (Tottenham); Kane (Tottenham), Maddison (Leicester), Rashford (Man Utd), Sancho (Borussia Dortmund), Sterling (Man City), Welbeck (Arsenal).
He has three goals and two assists for Leicester since a £20m summer move from Norwich.
"We'd have no hesitation in playing them in the games", Southgate said of Mount and Sancho.
Mount, now on loan from Chelsea at Derby, is another to have experienced football overseas, with the 19-year-old having spent last season at Dutch side Vitesse Arnhem.
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Dele Alli has been sidelined by a hamstring problem, while fitness doubts have seen the likes of Fabian Delph, Adam Lallana, and Jesse Lingard omitted.
"Jadon's is an unusual story for a young English player".
"He is a player that excites us a lot, he is adapting to a big football club and he has had two starts in the Champions League this year".
"Mason's is a slightly different situation". This year in the Championship he's created more chances than any other player in the league. We're always conscious of the balance in bringing young players in but we think they are performing well with their clubs and they are confident players.
Jadon Malik Sancho was born in London, England on March 25, 2000, which makes him 18-years-old.
Only nine have scored for England.