Kvitova will now quickly turn her focus to Wimbledon, where she won the title in 2011 and 2014, and hopes she will be able to play with less media pressure.
"I love being here and I love playing on this court, " Williams said.
"I'm happy with the game, of course", Kvitova said, "but I mean, it wasn't really about the game today". Now I can just enjoy everything - sometimes I just stand outside and see the sun and say, Oh, it s handsome.
The German's downward spiral continues as she suffered a fifth opening round defeat of the season, and she has now lost her last three matches on tour.
Mixing winners and unforced errors in nearly equal measure, Kvitova had three break points to go 4-0 up but Boserup saw them off, although she could not overturn all the advantage.
Her staggering longevity is illustrated by the fact that her potential second round opponent is compatriot Amanda Anisimova who, at just 15, is the youngest main draw competitor since 2005.More news: Venus Williams Marks 20th Anniversary with Victory
Kvitova, who reached the French Open semi-finals in 2012, will now take on Bethanie Mattek-Sands or Evgeniya Rodina in the next round.
World No. 1 Angie Kerber saw her nightmare season continue, as she was sent home from Paris without winning a match for the second year in a row.
That has left her old frailties exposed, with a weak serve broken six times by Makarova on Philippe Chatrier Court. I have the best memories which I can have. "Right now, I think that I have to find to myself again and just trying to forgot the clay-court season as soon as possible, and then reset and starting from the grass courts again".
Kvitova had made a quicker than expected recovery from the career-threatening injury sustained to her left, playing hand to compete at Roland Garros.
The two-time Wimbledon champion struggled to hold back the tears after beating 86th-ranked Julie Boserup of the United States 6-3, 6-2. "I'm really glad that we made this decision that I'm going to play here", Kvitova told the crowd during an on-court interview.
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That picture offers the starkest of contrasts with a spectacular 2016 that also brought her major wins in the Australian and US Opens and a runner-up spot at Wimbledon.
Svetlana Kuznetsova, the eighth-seeded 2009 champion, survived two time warnings to make the second round by seeing off Christina McHale of the U.S. 7-5 6-4.
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