The cover features 15 women, including teenage climate activist Greta Thunberg and New Zealand Prime Minister Jacinda Ardern, who through their work or personal experience have contributed to changing the world.
Inside the edition is a conversation between the duchess and US former First Lady Michelle Obama.
The edition, entitled Forces For Change, highlights "trailblazing change makers, united by their fearlessness in breaking barriers", Buckingham Palace said.
The magazine cover also features actors Jane Fonda, Salma Hayek Pinault, Laverne Cox, Yara Shahidi and Gemma Chan, alongside models Christy Turlington Burns, Adwoa Aboah and Adut Akech and radio presenter Jameela Jamil.
Diversity activist Sinead Burke, dancer Francesca Hayward, boxer Ramla Ali and writer Chimamanda Ngozi Adichie complete those pictured on the front.
There is a square in the middle of the magazine cover that acts as a mirror so that the reader feels "inspired" to improve their environment, according to a statement from the duchess.
Markle chose not to put herself on the cover, the magazine's Editor-in-Chief Edward Enninful said, as she felt it would be a "boastful thing to do", the BBC reported.
Markle will not be the first member of the British monarchy to appear in the publication as Duchess of Cambridge Kate Middleton starred on the cover in 2016.
Princess Diana featured on the cover three times and Princess Anne also appeared on the front in 1971 and twice in 1973.
Markle, who became a mother in May when she gave birth to Archie Harrison Mountbatten-Windsor, worked for seven months on the project "to take the year's most-read fashion issue and steer its focus to the values, causes and people making impact in the world today".
On the inside pages of the magazine, Markle has interviewed British primatologist Jane Goodall and her own husband Prince Harry.
In a message to the readers, released ahead of the magazine's publication on August 2, the duchess said: "Through this lens, I hope you'll feel the strength of the collective in the diverse selection of women chosen for the cover as well as the team of support I called upon within the issue to help bring this to light."
"I hope readers feel as inspired as I do, by the forces for change they'll find within these pages."
( With inputs from IANS )