Williams, who was just left out of the seedings at No.37 in the world, actually had a lot going for her going into the match - not only had she beaten Makarova in straight sets in both of their previous meetings, she was also a phenomenal 27-3 in her career against left-handed players at Grand Slams.
And those stats seemed to be manifesting themselves early on in the match as Williams stormed through the first set, 6-2, and had a point to go up 5-4 in the second set - after dropping that second set she even had a 3-0 lead in the third. But Makarova kept clawing her way back and cutting down on her unforced, and after one last Williams error - her 56th of the match - Makarova came good, 26 64 64.
"She played really well, and I think my level was just a little bit too up and down," Williams said. "I think my error count was a little high. I haven't looked at the stats yet, so I don't know what the errors were or what the first serve percentage was - I have to look at that and evaluate the match afterwards.
"Losing any match is never any fun, especially in a major. I definitely wanted a different result."
There was one silver lining though - she won over 80% of her points at net, 20 of 24 to be exact.
"I have definitely been working on my volleys, and I think I was effective up there today," Williams said of her play in the forecourt. "I do like getting to the net. So I think that was a good step for me.
"I think it's pretty natural for me to move forward," the former World No.1 added. It's my mindset. But I think for everyone you kind of sometimes get tentative, so everyone has to keep moving forward."
And she was all class when asked about Makarova. "I have to give her a lot of credit. She was really determined and just kept playing hard. Anytime you're seeded, you really want to win the first round."
Williams, who will be competing in doubles this fortnight with sister Serena Williams, looked on the up after reaching the finals of Auckland two weeks ago - what does she need to do to keep on the up?
"I do play points really well, and then sometimes I don't put them together as well. I feel like I have to be patient with myself, because I really haven't had a chance to play that consistently. So I think I just have to be patient and keep going and just wait for it to keep coming together more and more."
Will she be back next year? "I love Australia," she said. "I'd love to come back."