Defoe, 34, has not played for the Three Lions since 2013 but has been drafted in following injuries to Harry Kane and captain Wanye Rooney. Despite Sunderland's troubles this season, the former Tottenham and West Ham forward has scored 14 goals in 27 Premier League appearances this term.
As reported by Standard Sport on Thursday morning, West Ham's Andy Carroll has been left out, while Arsenal forward Theo Walcott has also been overlooked.
Southampton pair Nathan Redmond and James Ward-Prowse have both earned their first senior call-ups.
Tottenham trio Kyle Walker, Dele Alli and Eric Dier have all bee included while Alex Oxlade-Chamberlain is Arsenal's sole representative.
Chelsea defender Gary Cahill and versatile West Ham man Michail Antonio are the other London based players to be recognised by Southgate.
THE ENGLAND SQUAD IN FULL
For the forthcoming matches against Germany and Lithuania
Fraser Forster (Southampton), Joe Hart (Torino, on loan from Man City), Tom Heaton (Burnley);
Ryan Bertrand (Southampton), Gary Cahill (Chelsea), Nathaniel Clyne (Liverpool), Phil Jones (Man Utd), Michael Keane (Burnley), Luke Shaw (Man Utd), Chris Smalling (Man Utd), John Stones (Man City), Kyle Walker (Tottenham)
Dele Alli (Tottenham), Michail Antonio (West Ham), Ross Barkley (Everton), Eric Dier (Tottenham), Adam Lallana (Liverpool), Jesse Lingard (Man Utd), Jake Livermore (West Brom), Alex Oxlade-Chamberlain (Arsenal), Nathan Redmond (Southampton), Raheem Sterling (Man City), James Ward-Prowse (Southampton);
Jermain Defoe (Sunderland), Marcus Rashford (Man Utd), Jamie Vardy (Leicester).