The 9-1 chance, trained by Adrian Keatley, was back in ninth at Newmarket when Minding won the English version earlier in the month.
But she beat the 4-11 shot by a head this time under Shane Foley, with Now Or Never 10 lengths back in third.
The winning filly was a bargain buy for her owners - snapped up for just over £12,000.
"It's a dream come true," said Foley.
After the defeat of Minding, trainer Aidan O'Brien O'Brien revealed she had hit her head against the starting stalls before the race.
"Ryan (jockey Moore) said that when he came in that she anticipated the gate, just before they came in, she banged her head, took the skin off the side of her head and her nostril and burst a sinus," he said.
O'Brien said he still hoped to get Minding to the Oaks at Epsom on 3 June, and had news on his team for the Derby a day later.
He said The Gurkha, who was favourite with some bookmakers, would miss the race and run at Royal Ascot instead.
"What a big Guineas weekend which demonstrated there are still fairytales to be had amongst the mega-rich that tend to dominate flat racing's highest levels.
"After being beaten in races at Leicester and Brighton, Jet Setting's little-known, but very much up-and-coming, trainer and his owners got her for a song and have won big, lowering some even bigger colours in the process.
"And, in the 2000 Guineas, 83-year-old veteran trainer Kevin Prendergast has been successful. Fantastic. Incidentally, that Prendergast winner, Awtaad, is sticking to mile races and won't go for the Derby."
Jet Setting shocked Minding to win the 1000 Irish Guineas and deny the odds-on favourite a Classic double.