Instead, it's the fourth time in the past seven years that she is out in the first or second round. They increased as the games elapsed in favor of Wozniacki who was on a runaway with the set.
When she came on to continue, the second seed took a 3-0 lead due to Makarova's unforced errors.
The Dane served 13 of 15 for points on serve outscoring Makarova 27-14 who had a dismal second serve winning just once on four attempts.
Russian world number 35 Makarova, who next faces Czech world number 66 Lucie Safarova, shrugged off Wozniacki's unflattering summary of her chances.
In the second round of the Australian Open in January, down a set and trailing 5-1, then 40-15 in the third, Wozniacki rallied to save match points against Jana Fett.
Asked what she thought of those remarks, Makarova laughed and replied: "Well, I don't know what to say".
The left-hander led 5-1 in the first set and though Wozniacki hit back to 5-4, Makarova held on to move ahead.
"I think she played above her level and really raised it and got a little lucky and played well when she needed to", sniffed Wozniacki who had lost to the 30-year-old in the second round of the US Open last year.
Makarova failed to display her consistent tennis and she soon found herself trailing 0-5 having won just 10 points compared to Wozniacki's 23. "Good for me. Thanks God!" she told WTA Insider.More news: North Korea says U.S. are like 'gangsters' after 'regrettable' nuclear talks
If she is able to right the ship and play deep into the draw in NY, the major where she's had the most success, or defend her title in Australia, Wednesday's loss might be remembered more for its quirks - the first Wimbledon rains, an infestation of flying ants and extra-long bathroom breaks - than for Wozniacki's defeat. This match was better than my first round.
"Physically I'm very fit right now, probably better than I have ever been before".
The 25th seed will face the victor of the match that followed her on Centre Court between Germany's Tatjana Maria and France's Kristina Mladenovic.
"I served a little more consistent", than in the first round, said Williams.
"I was really nervous, because you need to win this point".
British hope Katie Swan reacted to her straight-sets defeat by 29th seed Mihaela Buzarnescu. "No one is going out there and saying, 'Oh, I have to lose because I'm playing so-and-so today".
"I mean, it's the third round now. I want to be here to focus on tennis, not eating bugs", she said to the umpire.
American Madison Keys, seeded 10th, defeated Thailand's Luksika Kumkhum 6-4, 6-3 in 78 minutes. Unexpectedly, the former quarterfinalist came up with a attractive backhand victor followed by an ace to save herself from the brink. "I don't know if I've ever played her before, so it's always hard to play someone for the first time - I'm sure she's seen me play a lot".