Rising Czech star Pliskova triumphed 4-6 7-6 (9-7) 6-4, in a tough environment too, with the local crowd firmly behind Azarenka who is a popular figure in Australia after her two Grand Slam titles in Melbourne in 2012 and 2013.
Azarenka only had herself to blame, missing two match points in the second set, and she made nine double faults and 44 unforced errors.
A year ago Azarenka arrived Down Under hoping to successfully defend the Australian Open title but bowed out in the quarter-finals.
She suffered a foot injury that saw her miss most of the first six months of the year and then had a knee problem. Azarenka finally abandoned the season in September after playing just 24 matches all year and not winning a title.
She plummeted down the rankings and split up with her boyfriend Stefan Gordy.
Currently down at 42 in the rankings, Azarenka is at least now fully fit.
Monday’s match was her first since September and Pliskova was a difficult and dangerous first-round opponent, ranked 23rd in the world after winning two WTA title last year.
For a while it looked like old times for Azarenka. She jumped out to a 5-1 led in the opening set before the first signs of trouble came.
Pliskova reeled off the next three and although Azarenka took the set, she squandered her chances in the second before running out of puff in the decider.