The track sold 6.8 million downloads throughout 2012 to take the lead, while Carly Rae Jepsen's 'Call Me Maybe' finished second with sales of 6.47m, reports Billboard.
fun. came third with 'We Are Young' (5.95m), meaning the Top 3 songs each sold more copies than 2011's number one, Adele's 'Rolling In The Deep' (5.81m).
Elsewhere, Maroon 5 finish the year with the fourth best-selling song. The band's hit 'Payphone', which features Wiz Khalifa, sold 4.76m copies.
Nicki Minaj rounds off the Top 5 with her global hit 'Starships'. The RedOne-produced cut sold 3.98m copies in the US by the year's end.
Digital single sales in the US in 2012 were up 5% on 2011's figures. A record 1.336 billion tracks were sold last year, compared to 1.271bn the year before.
The Top 10 best-selling singles in the US in 2012 are as follows:
1. Gotye: 'Somebody That I used To Know' (6.8m)
2. Carly Rae Jepsen: 'Call Me Maybe' (6.47m)
3. fun.: 'We Are Young' (5.95m)
4. Maroon 5 ft. Wiz Khalifa: 'Payphone' (4.76m)
5. Nicki Minaj: 'Starships' (3.98m)
6. One Direction: 'What Makes You Beautiful' (3.89m)
7. fun.: 'Some Nights' (3.84m)
8. Kelly Clarkson: 'Stronger' (3.82m)
9. Psy: 'Gangnam Style' (3.59m)
10. Maroon 5: 'One More Night' (3.46m)
Watch the music video for Gotye's 'Somebody That I Used To Know' below: