Harry Maguire has been included in the England squad to face Iceland and Denmark in the Nations League next month.
There are maiden call-ups for Phil Foden, Mason Greenwood and Kalvin Phillips, while Raheem Sterling also features.
Manchester United captain Maguire was on trial on the Greek island of Syros on Tuesday, following his alleged part in an incident involving police while on holiday in Mykonos.
The 27-year-old spent last Thursday and Friday night in custody and denies all charges.
Maguire has established himself as Southgate's premier centre-back and was a key pillar in the England side that progressed to the semi-finals of the 2018 World Cup in Russia, scoring in the 2-0 quarter-final win over Sweden.
Sterling attended Usain Bolt's 34th birthday party last Friday, after which the eight-time Olympic champion announced he was self-isolating while awaiting the results of a coronavirus test, encouraging all others who had come into contact with him to go into quarantine.
Manchester City midfielder Foden enjoyed a breakthrough campaign in 2019-20, scoring eight goals and supplying nine assists in 38 appearances across all competitions.
The last of those came in a tireless showing in the false nine role as City beat Real Madrid 2-1 in the Champions League – the latest demonstration of the 20-year-old's versatility.
Greenwood, 18, scored 17 goals in all competitions in a breakout season for Manchester United, matching the record for a Red Devils teenager in a single campaign held by George Best, Brian Kidd and Wayne Rooney.
Midfielder Phillips was a key part of the Leeds United squad that earned promotion from the Championship as league winners under Marcelo Bielsa.
After narrowly missing out on the Premier League Golden Boot to Jamie Vardy, Danny Ings is rewarded for his 22-goal campaign with a chance to earn his second cap, almost five years after his England debut.
England squad: Dean Henderson (Manchester United), Jordan Pickford (Everton), Nick Pope (Burnley); Trent Alexander-Arnold (Liverpool), Eric Dier (Tottenham), Joe Gomez (Liverpool), Michael Keane (Everton), Harry Maguire (Manchester United), Tyrone Mings (Aston Villa), Kieran Trippier (Atletico Madrid), Kyle Walker (Manchester City); Phil Foden (Manchester City), Mason Mount (Chelsea), Kalvin Phillips (Leeds United), Declan Rice (West Ham), James Ward-Prowse (Southampton), Harry Winks (Tottenham); Tammy Abraham (Chelsea), Mason Greenwood (Manchester United), Danny Ings (Southampton), Harry Kane (Tottenham), Marcus Rashford (Manchester United), Jadon Sancho (Borussia Dortmund), Raheem Sterling (Manchester City).