The former Bayern Munich and Arsenal forward captained his country on the occasion of his 130th and final cap and blasted in the only goal of the game – his 49th for Germany - in the second half to give Joachim Low's side the win.
Podolski made a lengthy speech before kick-off after being honoured with an on-pitch presentation and a mosaic in the stands, but England threatened to spoil the party as they produced the better performance for much of the match.
Gareth Southgate's side looked comfortable in an experimental 3-4-3, in which Michael Keane was handed a full senior debut, and Adam Lallana hit the post before Dele Alli missed a one-on-one in an encouraging first-half display.
But Podolski - starting an international match for the first time in 859 days - thumped his side's first shot on target of the match into the net in the 69th minute, and although England pushed for a leveller, they were unable to muster the sort of comeback that saw them come from 2-0 down to win 3-2 in Berlin a year previously.
For England, the defeat was only their second in 17 away games, but Southgate will consider it a chance missed against a Germany side missing a number of stars including Manuel Neuer, Jerome Boateng, Mesut Ozil, Sami Khedira and Julian Draxler.
Jamie Vardy saw wishful calls for a penalty waved after jumping over goalkeeper Marc-Andre ter Stegen, as England pressed the Germany defence in encouraging fashion in the early stages.
England looked likely to cause problems from corners, with debutant Keane flashing a strike over and Eric Dier heading straight at Ter Stegen from two separate deliveries, but Lallana came within inches of breaking the deadlock when he strode beyond the hosts' back line only to place a low left-foot shot onto the base of the post.
Dier fired a free-kick over the crossbar as England continued to look the better side, and Alli wasted a glorious chance four minutes before the break when he shot straight at Ter Stegen after being given time and space to set himself in the box.
Julian Brandt saw a shot bobble just wide after Joe Hart flapped a corner towards the edge of the area, before Podolski came within inches of connecting with a clever Toni Kroos chipped pass, as Germany began the second half in the ascendancy.
Dier's cross-cum-shot was beaten away well by Ter Stegen and Alli saw a half-chance blocked at his feet as Germany again failed to deal with an England corner, before substitute Andre Schurrle showed some attacking impetus with a good run and shot that whistled wide from 20 yards out.
Moments later, Podolski - who had spent the game shooting from wherever the ball fell to him - brought the stadium to its feet in some style. Kroos and Schurrle combined well to provide space for Podolski 25 yards from goal, and he blasted home a left-foot shot that flew past Hart and into the top-right corner.
The 31-year-old received a standing ovation as he was replaced late on, as Germany saw out a useful win ahead of Sunday's World Cup qualifier with Azerbaijan. England, meanwhile, will now prepare to host Lithuania at Wembley.