Belfast was the home port for the start of the races and hosted a Tall Ships event attracting about 500,000 people.
The races begin five miles from Portrush at 10:00 BST on Monday.
The fleet will sail past Scotland's Outer Hebrides and the Shetland Islands before crossing the North Sea to its next stop in Aalesund in Norway.
Ninety sailing trainees from Northern Ireland are taking part in the opening sail to the Norwegian port, which could take up to a week.
The races are expected to finish in Aalborg in Denmark at the start of August.
The Tall Ships festival, which ran from Thursday to Sunday, was an "amazing success", according to Belfast City Council's Eamon Deeny.
"A couple of the ships said this was a world record for them in terms of the number of people that visited them on site, so that in itself speaks volumes," he said.
"Belfast has shown again that it can hold world-class events."
Sally Titmus of Sail Training International, the organisers of the races, said Belfast had "probably been one of the best ports" the event had visited.
"We would love to come back," she said.
"This is the third time we've been here, it's getting better every time and it can only get better again."
The Tall Ships races will start off the County Antrim coast on Monday morning, bringing five days of maritime events in Northern Ireland to an end.