Sales data from The Official Charts Company revealed that the singer's record-breaking album has edged ahead of Oasis's (What's The Story) Morning Glory?.
The Manchester band's 1995 LP has sold 4,555,000 copies to date, while 21 has notched up 4,562,000 sales.
ABBA's 1992 Gold - Greatest Hits took the number three slot with 5,046,000 sales, while Sergeant Pepper's Lonely Hearts Club Band by The Beatles is the second-biggest selling album with 5,059,000 copies.
Queen's Greatest Hits from 1981 heads the chart after selling 5,866,000 since its release.
Last year, Adele's second album was named as the biggest-selling UK LP of the 21st century. It has also spent 101 weeks in the Official Albums Chart Top 75 since its January 2011 release, including 23 weeks at number one.
21 has shifted 25 million copies worldwide so far.
Currently it is 2012's second-biggest selling album behind Emeli Sandé's Our Version of Events, having sold 784,000 in its second year of release.
Its second single 'Someone Like You' was recently named most popular karaoke song of the year.
Watch the video for Adele's 'Someone Like You' below: