The Lazio ace netted his 69th goal for his country just five minutes after coming off the bench in Mainz.
The Lazio foward came off the bench midway through the second half of the World Cup warm-up game in Mainz and headed home a cross from Lukas Podolski in the 76th minute to rack up his 69th international goal, moving him one ahead of Muller.
Klose, who was born in Poland, made his Germany debut as a substitute on March 24, 2011 and marked the occasion with a goal.
He struck again against Greece just four days later - despite being afforded just 33 minutes over the course of his first two international outings - and the goals just never stopped coming, particularly in major tournaments.
Indeed, after breaking Muller's Germany milestone, Klose will now have his sights firmly set on the World Cup record, which is currently held by Ronaldo.
The retired Brazil legend has netted 15 times in the finals but Klose is just two behind and, as his country's only recognised striker for this summer's tournament in Brazil, is almost guaranteed to feature in at least three group games.