After overseeing a pair of 2-0 wins over the Republic of Ireland and Finland last month, the 50-year-old was bidding to become just the second England manager to win their first three competitive games in charge after Fabio Capello.
Carsley could have also become the first manager to do so without conceding a single goal, and England had never lost to Greece in nine previous meetings, winning seven of them.
With Harry Kane not fit enough to start, there was the expectation that either Dominic Solanke or Ollie Watkins - both of whom are in-form in the Premier League - would fill the void as the central striker.
However, Carsley peculiarly opted to go without a recognised number nine, instead deploying all of Jude Bellingham, Cole Palmer, Phil Foden, Bukayo Saka and Anthony Gordon from the first whistle.
Carsley would "definitely" use striker-less setup again
Despite the wealth of attacking talent on show, England were toothless against Greece, who deservedly went ahead through Vangelis Pavlidis and had another few goals disallowed at Wembley.
A late response did arrive in the shape of Bellingham's first-time striker, but Pavlidis completed his brace to propel Greece to a hugely emotional win, circa 24 hours on from the news of George Baldock's death.
Speaking to ITV Sport at full time, Carsley did not regret plucking up the "courage" to experiment with a different system, one which he insisted is still an option in future games.
"We were second best for a lot of tonight, it is disappointing. You are going to get set backs and it's important we respond," the 50-year-old said. "We tried something different and tried to overload the midfield.
"We tried it for 20 minutes yesterday, we experimented, and disappointed it didn't come off. It's unrealistic to expect too much and we will have to try again. All the goals were from mistakes, which is disappointing.
"It is definitely an option going forward. When you have someone of Kane's quality though it rules it out when he is available. But in the future you have to have the courage and ability to try things. We tried something different. It doesn't change anything. My remit is to do the three camps."
Should Carsley give his failed experiment another go?
For some England supporters, seeing all of Saka, Bellingham, Foden, Gordon and Palmer in the same starting lineup may have been a dream come true after Gareth Southgate's reluctance to deploy such an offensive setup at the Euros.
However, unlike Ultimate Team on EA FC, real-life matches are not as simple as shoe-horning all of your best players into one starting lineup, and Carsley's decision to go without an out-and-out number nine backfired tremendously.
The Three Lions may have had 64% possession of the ball, but they only forced Greece goalkeeper Odysseas Vlachodimos into one save all evening, and Carsley hardly needs any more proof that this system should not be repeated.
Now three points behind perfect Greece in League B Group 2, Carsley and England are under pressure to respond when they travel to Finland on Sunday, but the Three Lions have suffered a worrying new injury blow ahead of that game.