Considering the calibre of her opponent, a 6-4 7-6(4) loss was not as demoralising as last year's defeat by Ukraine's Kateryna Kozlova.
But it continued a steep decline for the 21-year-old who also fell in round one at the Australian Open and has managed back-to-back wins just once in 2019.
The match statistics made grim reading for Ostapenko with 60 unforced errors to Azarenka's 19.
Two years after she held the world's media captive after a stunning final victory over Simona Halep, the world number 39 was asked just one English question following her defeat.
"I think I didn't play my best match today. But, of course, the opponent for the first round was, I think, one of the toughest in the draw," she said.
"I think I was rushing too much. Also the conditions were very tough. It was super windy."
While the Latvian looks to arrest the slide, two-times Australian Open champion Azarenka is heading in the right direction having risen back into the top 50 after giving birth to son Leo in December 2016.
"She's one of the players that you never know what's coming, and she doesn't really give a lot of rhythm," Azarenka said.
"For the first round, for me, that's something very dangerous because it's important to get into the rhythm, into the tournament. You need to find a way to win, and I felt that today that's what it was."
Despite all her experience it was the 29-year-old Belarussian who began the match in charitable fashion, opening with two double faults before watching two Ostapenko backhands flash by her.
She broke back in the next game but dropped serve for the third time in a topsy-turvy set to trail 4-3.
Ostapenko double-faulted four times in the next game to hand back the advantage, then twice more at 5-6 to surrender a scrappy opener.
She continued to mix flashing winners with unforced errors in the second, leading 4-2 but allowing Azarenka back in.
Ostapenko served for the set at 6-5 and led 30-0 only to offer up more free points to her grateful opponent.
In the tiebreak Azarenka brought up match point with a thumping forehand winner and another Ostapenko misfire ended the contest.
Azarenka, a semi-finalist in 2013, will now face world number one Naomi Osaka in another blockbuster clash.
(Reporting by Martyn Herman; Editing by Christian Radnedge and Toby Davis)
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