Ivan Cameron, who had cerebral palsy and epilepsy, died in hospital aged six in February 2009.
Mrs Cameron told the Times: "Ive dying is such a massive thing that everything else is irrelevant."
She also said it changed her husband's outlook. "I think it changed Dave's politics. It made him understanding, though he couldn't be too subjective."
David Cameron had been an MP for less than a year when Ivan was born in 2002, and became prime minister the year after Ivan died.
Mrs Cameron said: "From the moment he is born, you are living in a situation that is quite surreal and difficult to deal with.
"It is intense every day, in and out of hospitals... in a way, that prepared me for Dave being prime minister, because I was used to living and operating in a way that's not normal."
When Ivan died, she said, the outside world "became meaningless".
"Like anyone else in my situation, I just kept going. You have to deal with it, because you have no choice."
The Camerons have three other children; Nancy, born in 2004; Arthur, born in 2006; and Florence, born in 2010.
Mrs Cameron also spoke about her family's life in Downing Street.
"We tried to make the flat feel like a home.
"Dave would be combing the children's hair for nits before giving a speech in the evening."
They got their groceries delivered because there was no supermarket nearby - and if she forgot butter, she would have to go to a shop in Trafalgar Square.
"So I did plan quite carefully."
She also said she dreaded the official holiday photograph.
"At the last minute we would panic and think, 'Oh God, it's the holiday photo...
"I hated the holding-hands thing because it looked too romantic, so we overdid the cups-of-coffee-looking-wistful pose."
Mrs Cameron was speaking to the Times Magazine to promote her clothing brand Cefinn.
Before her husband became Prime Minister, she was creative director for Smythson, which makes luxury leather goods.
Samantha Cameron, the wife of the former Prime Minister, has said their son's death "overshadowed everything".