The internationally-acclaimed humanitarian used her front-page debut as an opportunity to discuss everything from her career to politics, and becoming a mother to twins, Ella and Alexander, in June last year.
But the interview is not short on fashion either: photographed by Annie Leibovitz at her marital home in Sonning, England, Clooney's wardrobe features outfits from Rosetta Getty, Oscar de la Renta and Johanna Ortiz.
Here are the 5 things people are loving about the interview.
1. The lack of George Clooney on the cover.
2. The celebration of Amal's academic achievements.
3. The acknowledgement Amal's life didn't begin when she came a celebrity.
4. The story about how she and her husband met.
5. And what happened on that safari.
The full Vogue interview is already available to read on their website.