Lazio striker Klose is tied with the legendary Gerd Muller at the top Germany's all-time goalscoring charts on 68 goals heading into the clash with Chile, but he has not played for his country since September.
A foot injury forced the 35-year-old to miss the FIFA World Cup qualifiers against the Republic of Ireland and Sweden and the friendlies with Italy and England.
But Klose is now fit and firing on all cylinders again and will be seeking a place in the record books when Germany welcome the South Americans to the Mercedes-Benz Arena in Stuttgart.
The former Bayern Munich man is one of four players to return to the fray, with former team-mate Bastian Schweinsteiger, Borussia Dortmund midfielder Kevin Grosskreutz and Arsenal forward Lukas Podolski also making their comebacks.
Germany are likely to be among the favourites to win the World Cup later this year given the wealth of talent at coach Joachim Low's disposal.
But, ahead of a tournament that will see Germany face Portugal, Ghana and United States in the group stages, Low has opted to shuffle his pack, affording four uncapped players the chance to stake a claim for place in the World Cup squad.
Hamburg's Pierre-Michel Lasogga is included after a season that has seen him find the net 12 times, while Augsburg attacking midfielder Andre Hahn has also been given the opportunity to impress.
Freiburg centre-back Matthias Ginter is named among the defenders, along with Sampdoria right-back Shkodran Mustafi, whose call-up comes after two seasons that have seen the 21-year-old establish himself with the Serie A side following his release by Everton in 2012.
The three-time world champions have never played Chile, and can expect a tough test against a team that enjoyed a fine World Cup qualification campaign.
Jorge Sampaoli's side qualified third behind Argentina and Colombia in the CONMEBOL zone, with their dubious reward a draw that sees them grouped with Spain, the Netherlands and Australia.
This visitors approach the clash having lost just two of their last 15 matches and have held their own in games against European nations in recent times, earning a 2-2 draw with Spain last September and beating England 2-0 at Wembley in November.
There are few surprises in Sampaoli's squad, which includes Barcelona forward Alexis Sanchez and Juventus duo Arturo Vidal and Mauricio Isla.
However, one shock call-up is that of Cardiff City's Gary Medel, who has been selected by Sampaoli despite only recently returning from a thigh injury.
Fiorentina midfielder David Pizarro misses out, along with defender Miiko Albornoz.
The Swedish-born 23-year-old was thought to be under consideration for the clash, but insists that despite failing to be called up he has not given up on his dream of making the World Cup.
"I was ready for the match against Germany, so I must work even harder here in Sweden to be called again," the Malmo defender told TERRA.
"I still have the dream of playing a World Cup with Chile, so we'll train well to be ready if they call me."
