Having last year reached the Wimbledon semi-finals, the Polish 20th seed was expected to beat Mayer and advance to the round of 16 for the first time in his second visit to Melbourne Park.
But after a tight contest for the first 10 games of the match in which games went with serve, Janowicz dropped serve in the 11th game and then lost the first set.
Mayer would eventually win 15 of the last 19 games of the match to get to the fourth round of the tournament for the first time himself, leaving Janowicz to curse a foot injury following the 7-5 6-2 6-2 loss.
"I was able to play Paris Bercy normally but I came back to my home, and after two days I was just walking on the street and I starts to feel the pain and this was the beginning," said Janowicz, who expected the problem to clear only to be told following an MRI a week later he had a broken bone.
"Before I left Poland (it) was still a little bit broken, it was not 100 per cent healthy.
"There was still quite a bit inflammation.
"Most important was I didn't practice for two months, I just came to Sydney without absolutely any practice, and I didn't have the opportunity to prepare myself for long matches."
Janowicz added that having had little preparation ahead of a first-up loss to Alexandr Dolgopolov in Sydney last week, his cause against Mayer was not helped either by long matches against Australian Jordan Thompson and Spaniard Pablo Andujar.
"My problem today was I was unprepared, yeah, and I played two matches in a row over three hours," he said.
"Second round (against Andujar) three hours 30 minutes, I believe, and (it) was extremely hot.
"I was really exhausted after this match.
"Because I didn't practice much, I was not able to get ready for the next match.
"Today I was completely kaput."