The collection sold 4.41 million copies in the US during 2012, taking it to the top of the year-end tally and marking the first time an artist has achieved the feat since records began in 1991.
Adele managed to outsell her nearest rival by over a million copies, as Taylor Swift's Red lands at two with sales of 3.11m, reports Billboard.
One Direction landed in third place with their debut album Up All Night (1.62m), while their follow-up Take Me Home clocked in at five (1.34m).
The boyband mark the first time an act has had two of the year's top five best-sellers since SoundScan starting tracking sales in 1991.
Elsewhere, Mumford & Sons land in fourth place with Babel tallying up 1.46m sales in the US during 2012.
It means that four out five of the best-selling albums in the United States last year were released by British artists.
The Top 10 best-selling albums in the US during 2012 are as follows:
1. Adele: 21 (4.41m)
2. Taylor Swift: Red (3.11m)
3. One Direction: Up All Night (1.62m)
4. Mumford & Sons: Babel (1.46m)
5. One Direction: Take Me Home (1.34m)
6. Justin Bieber: Believe (1.34m)
7. Carrie Underwood: Blown Away (1.2m)
8. Luke Bryan: Tailgates & Tanlines (1.1m)
9. Lionel Richie: Tuskegee (1.07m)
10. Jason Aldean: Night Train (1.02m)
Watch the music video for Adele's 'Rolling In The Deep' below: