In just over 10 months since it went on sale, the disc has overtaken the late star's 2006 second album, which previously took the title back in August.
The landmark comes at the end of a cracking year for the Londoner.
To date, 21, which includes hit records including Someone Like You and Set Fire To The Rain, has passed sales of 3.4 million copies in the UK, eclipsing Back To Black which has sold 3.3million.
Since going on sale in January the disc has never left the Top 10, and yesterday clocked its 45th week there.
Yesterday it climbed from Number 9 to Number 5, undoubtedly spurred on by the London singer's six Grammy nominations.
The Londoner is a front-runner in categories including Album Of The Year, Record Of The Year, and Best Pop Vocal Album.
In a message posted on her blog over the weekend, the singer - who had an operation on her voice last month - said she was "lost for words" at the Grammy recognition.
She said: "Thank you so much to the academy for nominating this record for 6 Grammys!!!
"This has been the best year as it is but to end 2011 with this incredible achievement and honour is beyond anything I can express.
"Thank you to every single person who has taken a shining to this record, for making it have such an impact, this record has taken on a life of its own thanks to you. I made the record and you've made it what's it's become."
Adele has also achieved much success across the glove, topping the charts in more than 20 countries including the United States, Ireland and France.
She's also won countless awards this year, including three American Music Awards, a MOBO gong and four MTV prizes.