The birth of the new heir was announced by Kensington Palace.
"Her Royal Highness The Duchess of Cambridge was safely delivered of a son at 4.24 p.m.," the palace said in a statement. "The baby weighs 8 lbs. 6 oz. The Duke of Cambridge was present for the birth.
"The queen, The Duke of Edinburgh, The Prince of Wales, The Duchess of Cornwall, Prince Harry and members of both families have been informed and are delighted with the news," the statement said. "Her Royal Highness and her child are both doing well and will remain in hospital overnight."
"We could not be happier," Prince William said in a short statement released by the palace. He will be spending the night in the hospital with his wife and new son.
The annoncement came after Middleton had been in the hospital for more than 14 hours, though the baby was born several hours before the birth was announced.
Cheers erupted at St. Mary's Hospital, where the baby was born, and Buckingham Palace when the announcement was released.
Throngs of people gathered outside of the palace to wait for the formal, signed birth announcement that was driven from the hospital to the palace. Following tradition, the document was taken into the palace to be shown to the queen before it was placed on an easel in the palace court.
The newborn is third in line to the British throne after his grandfather, Prince Charles, and father, Prince William. The reigning monarch, Queen Elizabeth II, has been on the throne 61 years. The baby is the queen's third great-grandchild.
"The Queen and Prince Philip are delighted at the news of the birth of The Duke and Duchess of Cambridge's baby," the British monarchy's official Twitter account posted.
Prince Charles expressed his joy about being a first-time grandfather.
"Both my wife and I are overjoyed at the arrival of my first grandchild," Prince Charles said in a statement. "It is an incredibly special moment for William and Catherine and we are so thrilled for them on the birth of their baby boy."
"Grandparenthood is a unique moment in anyone's life, as countless kind people have told me in recent months, so I am enormously proud and happy to be a grandfather for the first time and we are eagerly looking forward to seeing the baby in the near future," Prince Charles said.
The world's intense interest in the Duke and Duchess of Cambridge's real-life fairy tale extended to Middleton's pregnancy and the baby long before it was born.
"You have this gorgeous young couple," ABC News royal contributor Victoria Murphy told ABCNews.com. "He's a prince and she's a commoner, and they get married and this is their first baby -- so it's like the completion of the fairy tale, and I think people find that really fascinating.
"There's a lot of fascination internationally in the British royal family just because it's such an established institution and people find it quite quaint," Murphy said. "People are just generally really curious about it because it's not something that exists in every country."
Every moment leading up to the delivery has been closely scrutinized, including the royal bump, her pregnancy fashion and every baby-store shopping trip.
"It's the fascination and joy everybody feels when a baby is born and then, for British people certainly, the renewal of the monarchy," Robert Lacey, author of the book "Majesty," told ABCNews.com.
"We know that this new baby ... is our sovereign who will be our figurehead by the end of this century, maybe even into the next century," he said.
The British Parliament is changing a 300-year-old law so that William and Kate's firstborn, regardless of gender, would be the heir to the throne.