It has sold more than two million copies in the US and Canada, according to NPD BookScan data.
The sales figures were announced by Penguin Random House on Friday.
The publisher says the book is also a bestseller in many other countries including Australia, the UK, France, Germany, Korea and South Africa.
The book is a window into the personal life of the Obamas prior to, throughout, and following their time at the White House as the first African-American first lady and the first black US President Barack Obama.
In it, Mrs Obama reveals difficulties in her marriage with Barack, disclosing details of how the couple suffered a miscarriage and later used in vitro fertilisation (IVF) to conceive both children, Malia and Sasha.
The 54-year-old also criticises US President Donald Trump, writing that she can "never forgive" him for "putting my family's safety at risk" over his championing of the "birther" theory that her husband was not born in the US and thus was not a legitimate president of the US.