The Pole was given a lesson in claycourt tennis from former champion Svetlana Kuznetsova, the Russian winning 6-1, 6-2 in third round action.
Sharapova swept aside Japan's Ayumi Morita 6-1, 6-1 in what was a second round match held over from Thursday because of the marathon clash between Paul-Henri Mathieu and John Isner.
The second seed, who won on clay in Stuttgart and in Rome in the buildup to Paris, will have a one-day turnaround before taking on China's Peng Shuai for a place in the last 16.
Top seed Azarenka was on late in the day, re-scheduled to Court One, and she hammered out a 6-4, 6-4 win over Canada's Aleksandra Wozniak just before sunset.
Radwanska was the highest seed to fall in the tournament so far as she had no answer to the all-court game of Kuznetsova, who won at Roland Garros in 2009, five years after she won the US Open, her only other Grand Slam title.
Since then, the Russian has had a torrid time with injuries and loss of form, while Radwanska has smoothly made the transfer out of the junior ranks and up the WTA rankings, winning three tournaments this year already.
But all that was cast aside as the Russian took command of the match from the start with a 5-0 lead and offered her opponent no chance after that to get back into it.
"I have not played so well in a long time, so I am really happy about that," Kuznetsova said.
"I have not had this feelng for quite a time. I have started to do things the right way off the court in practice. I am confident I am getting back to my game that brought me the victories I had."
There was no such revival in fortunes for Ana Ivanovic, another former champion at Roland Garros who has found the going tough since her triumph in 2008.
The Serb, a former world number one, but seeded just 13th this year, looked comfortable in the first set against claycourt specialist Sara Errani, but her game started to unwind in the second as the little Italian retrieved everything that came her way to run out a 1-6, 7-5, 6-3 winner.
Errani, who has won three claycourt titles this year already, will next take on Kuznetsova with the prize for the winner being a place in the quarter-finals.
Australian sixth seed Samantha Stosur, the runner-up here in 2010, coasted past Russia's Nadia Petrova 6-3, 6-3 and will next play American teenager Sloane Stephens.
Stephens kept the Stars and Stripes flying in the tournament with a third round 6-3, 6-2 win over Mathilde Johansson, the last Frenchwoman left in the draw.
The Florida youngster was one of just three Americans to make it into the third round along with Christina McHale and Uzbekistan-born Varvara Lepchenko, following the early exits of Serena and Venus Williams.
For 19-year-old Stephens it was the first time she has reached the last 16 of a Grand Slam tournament in four appearances, ensuring she will continue her rise up the world rankings.
Asked about the influence on her of the Williams sisters, Stephens replied: "Yeah, they definitely inspire.
"I mean - race has nothing to do with it - but they inspire everyone to play tennis.
"They're two of the best tennis players to ever play the game.
"I think they're a really great inspiration to everyone. I like them. I think they're funny."
Other qualifiers in the top half of the draw for the last 16 were 15th seed Dominika Cibulkova of Slovakia who defeated Maria Jose Martinez of Spain 6-2, 6-1 and Petra Martic of Croatia who beat Anabel Medina Garrigues of Spain 6-2, 6-1.
Late in the day 10th seeded German Angelique Kerber maintained her challenge with a 4-6, 6-3, 6-2 win over Flavia Pennetta of Italy.
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