The 29-year-old Australian, who hopes to qualify for next year's Olympics, started well with the butterfly leg before losing ground on the backstroke and then struggling with the breaststroke as he finished second-last in an event he rarely swam prior to retirement.
"I'm really pleased with the first 50, the fly leg was great, the backstroke was great and I'm really happy with the underwater work tonight," Thorpe told reporters.
"I was doing really well and then the breaststroke happened. It wasn't so bad this morning. It is something I can work on."
South African Chad Le Clos, 19, won the race with a time of 53.06 seconds, with Thorpe three-and-a-half seconds back in one of the worst results of his illustrious career.
"I looked up to him growing up, his career talks for itself," Le Clos said of Thorpe.
"I don't know if you can call it a win, exactly, because he is still obviously nowhere near his best but, to beat him, I'll take it."
Earlier, Thorpe, despite complaining of suffering more nerves than usual, had said he was happy with his sixth-place finish across the heats in his first race back.
Before the final, Thorpe looked far more relaxed as he smiled his way through what appeared to be a light-hearted conversation with Austrian Markus Rogan before taking of his blue T-shirt to reveal his impressive physique.
"A lot more relaxed this evening," Thorpe said. "A little more nervous than what I would consider normal but at what is a completely acceptable amount."
The lanky Thorpe, with the huge, flipper-like feet, will take part in the 100m butterfly on Saturday as continues his preparations to try to qualify for the 2012 Games in London at the Australian Olympic trials in March.
Australia's most successful Olympian is expected to struggle again in Saturday's event but the individual medley and butterfly disciplines are highly likely to be ditched for the freestyle on which he built his name.
His struggles in the glamour-free surroundings of the Singapore Sports School in front of a few hundred cheering spectators highlighted the tough task he faces in reaching another Olympics with little training time and competitors a decade younger than him.
"People want to see me do well and see me do well quickly. I prefer to do that, I prefer not to wait," Thorpe said.
"I haven't swum for a long time. I have to take stock where I was 12 months ago to where I am now. I'm in a final and competing reasonably well. I'm happy.
"Hopefully with a little more time we can have some good performances."
Another returning Australian to struggle was Libby Trickett. The triple Olympic champion finished last in the final of the 100 metres butterfly and sixth in the 50m freestyle in her first international meet since the 2009 world championships.
Despite the results, the 26-year-old was confident of performing well in the Olympic trials.
"I think I'll be ready in time for March. I know that I'll keep moving forward and this is just one step along the way."