Azarenka, last year's Australian Open champion and a winner of this tournament in 2009, made light work of quarter-final opponent Ksenia Pervak on Saturday, beating the Kazakh player 6-1 6-0.
Pervak knocked out former world number one Caroline Wozniacki in the first round but had no answer to the current rankings leader as she made a rapid exit.
Awaiting Azarenka in the last four is third seed Williams, the reigning Wimbledon and Olympic champion, who is eyeing a fifth Australian Open title later this month.
Williams' tune-up for Melbourne Park continued with a hard-earned 6-4 6-3 success against fellow American Sloane Stephens.
There is a mutual admiration and friendship between Stephens, 19, and 31-year-old Williams, which both players have outlined this week.
Williams remains the more formidable player of the two, but Stephens has entered the top 40 and is expected to climb higher.
Watch: Serena and Azarenka though in Brisbane... More Videos
While Williams and Azarenka duke it out for a place in the Brisbane final on one side of the draw, the other semi-final will be contested by Russian Anastasia Pavlyuchenkova and Ukrainian Lesia Tsurenko.
Unseeded Pavlyuchenkova claimed a fine win over fourth-seeded German Angelique Kerber, coming through 7-6 (7/3) 7-6 (7/3). Tsurenko prevailed 6-4 6-4 against Slovakian Daniela Hantuchova.