The judges acknowledged the mum-of-three's charity work for making headlines over and above her fashion choices.
"She used the pandemic to launch major campaigns around early-years development and continue her work trying to lift the stigma around discussing mental health, as well as supporting those living with childhood trauma," they wrote.
Kate Middleton continued her charity work over video calls amid the pandemic.
Meghan Markle missed out on a spot in 2020 after being named one of the world's most influential women two years in a row, with the Queen taking the coveted ranking last year.
But this year the duchess has made the list once again, with editors noting, "No woman has been more talked about on these shores in the past 12 months than Meghan, the Duchess of Sussex.
"Now living in California, after stepping back from life as a working royal [and post that interview], her sights are firmly set on making positive waves in public life.
"In addition to her extensive philanthropy work, she inked Netflix and Spotify deals and authored a children's book, all with a shared goal of promoting equality. What will she do next?"
The mum-of-two celebrated her 40th birthday last week, using it as an opportunity to launch her new mentorship programme for women.
Other well-known women on the list include director and writer Emerald Fennell, who played Camilla Parker Bowles on Netflix's The Crown, and designer Vivienne Westwood.
Meghan Markle's own guest-edited issue of the magazine hit stands exactly two years ago.
Meghan's "Forces for Change" issue was Vogue's fastest-selling issue of all time, selling the most copies in over a decade.
The Vogue 25
Cassandra Russell, head of fashion, luxury & retail brand partnerships (EMEA), TikTok
Charlie Martin, racing driver
Charlotte Mensah, hairstylist
Debbie Hewitt, chair, the Football Association
Emerald Fennell, writer and director
Emma Paterson, literary agent
FKA Twigs, musician
Jade Fadojutimi, artist
Jane Fraser, CEO, Citigroup
Joanne Anderson, Mayor of Liverpool
Joeli Brearley, founder and CEO, Pregnant Then Screwed
Kate Bingham, chair, UK Vaccine Taskforce
Kate Winslet, actor
Margot Henderson, chef
Marina Hyde, journalist
Nicola Sturgeon First Minister of Scotland
Phoebe Dynevor, actor
Priya Ahluwalia, fashion designer
Rosamund Kissi-Debrah, activist
Soma Sara, Founder, Everyone's Invited
Sulinna Ong, head of music (UK & IE), Spotify
The Duchess of Cambridge
The Duchess of Sussex
Vivienne Westwood, fashion designer
Zara Mohammed, secretary general, the Muslim Council of Britain
