Michael McKillop's 13-year unbeaten run in Paralympic competition ended as he finished fourth in the T38 1500m at the World Para-Athletics Championships.
Canadian Nate Riech, tipped to challenge the Irishman in Dubai, delivered impressive to dominate Friday's race as he won in 4:02.04.
McKillop, 29, finished in 4:09.07 despite his strong closing 100 metres.
Algeria's Abedelkrim Krai was second in 4:04.70 with Australia's Deon Kenzie third - 0.58 ahead of McKillop.
McKillop, born with a mild form of cerebral palsy, has won four Paralympic titles and nine world gold medals during a glittering career and his last defeat came over 1500m at the 2006 World Championships in Assen.
The Glengormley athlete's Irish team-mate, Belfast man David Leavy, produced a personal best time of 4:23.86 to finish ninth.
Leavy's time cut 1.49 seconds off his previous best time.
McKillop boxed in at crucial moment
McKillop remained in the middle of the pack over the opening 400m as Denmark's Anders Lagergren and Namibia's Petrus Karuli produced a searing early pace.
Inevitably, the early leaders were caught by the 700m mark and at that stage, McKillop found himself boxed in as Riech began to produce a move which ultimately proved decisive.
As McKillop attempted to manoeuvre himself into a better position with two laps to go, his stride was broken as he was clipped by another athlete and by that stage, Riech was away and gone.
McKillop remained a distant fifth with just over 100m left and while he was able to pass another Canadian Liam Stanley in the home straight, a medal proved beyond him as he crossed the line in fourth.
The Northern Irishman's time was 1.08 seconds inside his own T37 category's championship record set in Lyon in 2013 but it didn't prove enough to earn him a medal.
Injury problems catch up with McKillop
McKillop's career has been beset by injuries since he won two gold medals at the London 2012 Paralympics.
After winning two world titles in London in 2017, he was forced to miss the entire 2018 season because of a groin injury.
Speaking after Friday's race, McKillop said his injury problems in recent years had finally caught up with him.
"I prepared as best I can but I knew that I wouldn't be able to go with the pace from a long distance out," he told Paralympics Ireland.
"I've just had eight months in my legs, that's it.
"If I can do that in another eight months, another year or just below a year on top of this it will get me back in the medals and hopefully back on top of the podium.
"Tonight wasn't my night, that's sport for you. The better people beat me," added McKillop, who has also spoken of his mental health battles in recent years.
Leavy, meanwhile, said he was "ecstatic" with his personal best performance.
"Coming in here ranked 13th or 14th all season's best and to come out and put in a performance and finish ninth, there's nothing I could have done and I feel really pleased with the performance I put in."