Azarenka competed at the 2012 Australian Open as the third seed, defeating Heather Watson, Casey Dellacqua, Mona Barthel and Iveta Benesova in the first four rounds without dropping a set, losing just 10 games and winning 48. In the quarterfinals, Azarenka faced a sterner test against World No. 8 Agnieszka Radwańska, and lost the opening set on a tie-break before coming back strongly, losing just two futher games en route to a 6–7, 6–0, 6–2 win. In the semi-finals, she defeated the eleventh seed and defending champion Kim Clijsters 6–4, 1–6, 6–3 to reach her first Grand Slam singles final where she faced the World No. 4 and 2008 Australian Open champion, Maria Sharapova, conqueror of 2011 Wimbledon champion Petra Kvitová in the other semi-final. In a nervous start to the final, Azarenka lost the opening two games of the match, and was within two points of trailing 0–3 after Sharapova took the first two points of the third game. Azarenka came back to hold serve, however, and took the next two games to establish a 3–2 lead, before her opponent held serve to level the score at 3–3. This would prove to be Sharapova's last service hold in the match, as Azarenka then proceeded to win all of the next nine games (breaking the Sharapova serve on four consecutive occasions), to record an emphatic 6–3, 6–0 victory. Unusually, due to the earlier quarter-final defeat of Caroline Wozniacki by Clijsters in the same tournament, whichever of the finalists triumphed in Melbourne would gain sufficient points to replace Wozniacki at the top of the Women's rankings. Azarenka thus recorded her first Grand Slam singles title and became the World No1 (with effect from the 30th of January 2012) in the same match.
Her first tournament as world number one was the 2012 Qatar Total Open. After receiving a bye in the first round, she played German Mona Barthel in round 2, dropping just one game in a comprehensive 6-1 6-0 victory.