Germany captain Manuel Neuer has been ruled out of Wednesday's home friendly against England while die Mannschaft's shooting-star Timo Werner is set to make his debut.
A calf injury has sidelined Bayern Munich goalkeeper Neuer, who misses both the friendly against Gareth Southgate's Three Lions in Dortmund and Germany's 2018 World Cup qualifier against Azerbaijan in Baku on Sunday.
Paris Saint-Germain's shotstopper Kevin Trapp has been called up to take Neuer's place for both internationals.
Up front for Germany, the 21-year-old Werner is set to feature against England.
Germany have struggled to settle on a striker to replace all-time top-scorer Miroslav Klose, who scored 71 goals in 137 internationals, and retired after they won the 2014 World Cup in Brazil.
"I do wonder where the next Miroslav Klose is?" Germany's head coach Joachim Loew asked a year ago before adding Klose to his coaching staff.
"Where is the striker, who plays in the middle, who is quick, has a strong header and is dangerous in front of goal?"
Loew believes he has his answer and wants to blood Werner with one eye on June's Confederations Cup in Russia.
The 21-year-old fleet-footed striker drew the attention of Loew, and Liverpool, according to reports, with a series of dynamic performances and has so far bagged 14 goals for Leipzig in their first Bundesliga season.
Loew says Werner has the potential to be world class and will test his rising star against England.
Werner admitted he nearly crashed his car when the Germany call-up came.
"I had to be careful not to tear the wheel off," Werner told Die Welt.
"I had just been shopping and had to pull over.
"If I play in my first international, it will be an honour."
As Loew breaks in a new striker, he will be waving goodbye to Galatasaray's Podolski.
The international England friendly doubles as swansong for Podolski, who retired from international football last year, but has been called up for a farewell appearance.
The 31-year-old has scored 48 goals in 148 appearances for Germany, but has not held down a first-team place since the Euro 2012 finals.
Loew is likely to start with Mario Gomez, who has scored for Wolfsburg in his last three games, with RB Leipzig's Werner either alongside him or coming off the bench with Podolski on the wing.
When the European powerhouses last met, Germany raced into a 2-0 lead in Berlin last March, with goals by Toni Kroos and Gomez, before Harry Kane, Jamie Vardy and Eric Dier scored to seal England's 3-2 comeback win.
As well as Neuer, Loew is without winger Marco Reus, who is sidelined with a hamstring injury, while World Cup-winner Mario Goetze is recovering from a metabolism disorder.
Loew will experiment in Dortmund, then name a full-strength side for Sunday's Russia 2018 qualifier against Azerbaijan, the same day England host Lithuania at Wembley.
The Germans are five points clear at the top of Group C, but Azerbaijan are their closest rivals with seven points alongside Northern Ireland, while England are two points clear at the top of Group F.