The 95-year-old praised the “commitment, dedication and adaptability” of the competitors after the games were delayed by 12 months due to the coronavirus pandemic. The Queen added the Paralympics has been “inspirational” and “performances have lifted the nation”.
Her message came after Team GB retained second place on the medal table – only behind China.
They brought home 124 medals, including 41 gold, 38 silver and 45 bronze.
In a statement, the Queen said: "I offer my warm congratulations to Paralympic athletes from Great Britain and Northern Ireland, and indeed to the athletes of all Commonwealth countries, on their enormous success at the Tokyo Games.
"The commitment, dedication and adaptability shown by you, and your support teams, during the exceptional circumstances of the last 18 months, has been inspirational.
"Your performances have lifted the nation and your triumphs been celebrated by us all.
"I send my very best wishes to all those who have contributed to the success of these memorable Games."
The Duke and Duchess of Cambridge also paid tribute and praised the “mental strength, determination and talent” demonstrated by those who took part.
Prince William and Kate also gave a special mention to the charity Sports Aid for their efforts in helping competitors realise their dream.
“Without this support, these athletes may not have had the financial support and recognition they require to perform at the level they do.”
Team GB won medals in 18 of the 19 sports athletes competed in, only missing out on a podium position in shooting.
Boccia champion David Smith led the handful of British athletes still in Tokyo on Sunday for the closing ceremony.
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Sprinter Thomas Young, cyclist Benjamin Watson and swimmers Maisie Summers-Newton and Reece Dunn were among the emerging talent to burst on to the scene to take gold, with 56 British debutants claiming medals.
Team GB fell 23 medals short of the 147 achieved at the Paralympics in Rio five years ago – but this figure may be inflated due to the absence of Russian athletes.
But, the tally in Tokyo is higher than the 34 golds and 120 overall medals won at London 2012.