Die Mannschaft found themselves 2-1 down inside a frantic opening 22 minutes at the Volkswagen Arena, with Leroy Sane making the net ripple in between strikes from Japanese duo Junya Ito and Ayase Ueda.
Flick's decision to make five substitutions during the second half, including a debut handed to 32-year-old Pascal Gross, failed to change the dynamic of the contest, and it was instead two Japanese substitutes, who ply their trade at club level in Germany, that sealed victory for the visitors.
Takefusa Kubo unselfishly set up VfL Bochum attacker Takuma Asano for a simple tap-in on the 90-minute mark, before Fortuna Dusseldorf midfielder Ao Tanaka rubbed salt into Germany's wounds just 72 seconds later with a header into the bottom corner.
A chorus of boos and "Hansi out" chants rang around the Volkswagen Arena as Flick walked down the tunnel at full time, with the former Bayern Munich boss seemingly hanging onto his job by a thread.
After winning each of his opening eight games in charge of Germany by an aggregate score of 33-2, Flick has since won only four of his last 17 internationals in all competitions, and Die Mannschaft have subsequently dropped down to 15th in the FIFA world rankings.
Last year, Germany picked up just one win out of six games in their UEFA Nations League group, before suffering an embarrassing group-stage exit at the 2022 World Cup, losing to both South Korea and Japan.
Germany's latest defeat against Japan has extended their winless run to five games, including four losses, and although Flick has acknowledged that improvements need to be made quickly, the 58-year-old is adamant that he is the right person to lead the national team when they host Euro 2024, and believes it "doesn't help to point fingers now".
"We and the coaching staff are trying everything. I think we are doing well and I am the right coach," Flick told reporters after the match as quoted by bulinews.com.
Commenting on the defeat to Japan, Flick said: "We are really disappointed. You have to admit that Japan is a good team. We don't have the tools right now to beat a defence like that.
"The team tried again and again, then there were individual mistakes, which Japan then exploited and deserved such a big win.
"We were not in a position to beat a team like that. They have the basics. We in German football have to wake up. It's clear that the disappointment is huge. We're disappointed too.
"We have different positions where we need to improve. It doesn't help to point fingers now. We've really been hit over the head. Now we have to shake ourselves up and do better against France."
Germany will seek to return to winning ways when they face a challenging friendly encounter against World Cup runners-up France at Westfalenstadion in Dortmund next Tuesday.