The 27-year-old trailed Mito Pereira ahead of Sunday's finale, but carded a closing three-over-par 73 to miss out on the play-off between Will Zalatoris and eventual winner, Justin Thomas.
Fitzpatrick was the only player in the event to shoot under par in each of the first three rounds.
What's more, even a level-par 70 in the final round would have sealed his place in history books by becoming the first English winner of the US PGA in over a century.
Looking back, the former Ryder Cup player said: "Having had a chance to reflect, it's been a tough one to take. Of course everyone this week has stories of what they could have done differently to have a better outcome.
"But for me to come away from the week to miss the play-off by two shots hurts a hell of a lot.
"I felt I was always chasing my tail right from the first tee shot on Sunday, I never quite felt I had my ball under control off the tee and that constantly put me out of position to challenge.
"Yes I made a few mistakes and I hit some poor shots at the wrong times and that's what makes it hurt even more because I know I can hit better shots than I did yesterday.
"I'll reflect on my week some more and get back to practising for the next stretch of events. Thank you to everyone for your support, I really do appreciate it!"
After his fifth placed finish, Fitzpatrick was moved up the world rankings to number 15. Plus, he was among 27 players to be officially confirmed for next month's US Open at Brookline.
The Englishman won his 2013 US Amateur at that same course, and he will eye a repeat of that result as he continues to fight for his first major.