The 15-year-old, dressed in a striped T-shirt and navy trousers, bid farewell to her parents and her younger sister, Infanta Sofia, 14, as she prepared to board her flight from Adolfo Suarez Barajas Airport in Madrid.
Leonor will study for her International Baccalaureate at the UWC Atlantic College in Llantwit Major, Wales, for the next two years.
WATCH: The next generation of young royals
Queen Letizia, wearing a grey ensemble, was pictured embracing her daughter in a hug before Leonor passed through the departure gate.
The princess, who is the heir to the Spanish throne, also hugged her father goodbye and they appeared to smile at one another under their face coverings.
Princess Leonor hugs her father King Felipe
Leonor carried her three pieces of luggage, including a tan satchel, a large backpack and a carry-on suitcase as her family waved her off.
The Spanish royal family waved off Leonor at the gate
The Dutch royal family shared a photo of Alexia as she prepared to leave for the UK, also on Monday.
The image, taken by the king, showed the young royal wearing a red and black checked jacket with ripped pale blue jeans and white trainers as she held two large bags and a face covering outside the royal family's home, Huis ten Bosch Palace, in The Hague.
King Willem-Alexander shared a photo of daughter Princess Alexia
UWC Atlantic College is set in the 12th century St Donat's Castle on the southern Welsh coast and campus facilities include a library, woodland, an indoor and outdoor swimming pool, and classrooms within historic buildings.
It was founded in 1962 by German educationalist Kurt Hahn, who also set up Gordonstoun boarding school in Scotland, famously attended by Prince Charles.
Notable alumni include King Willem-Alexander and Princess Raiyah bint Al-Hussein of Jordan. Princess Elisabeth of Belgium, 19, also graduated from the college in May 2020.
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