A tournament of upsets got the biggest of the lot as defending champion Serena Williams sensationally lost to Spaniard Garbine Muguruza in the second round.

Williams' 6-2 6-2 defeat was her worst in terms of scoreline in her 16-year grand slam career and will send shockwaves through the tournament, which lost Australian Open champions Stan Wawrinka and Li Na in the first round.

Like Rafael Nadal on Monday, Williams was sent out to Roland Garros' second court, Suzanne Lenglen.

But, while her fellow defending champion barely broke sweat in beating Robby Ginepri, Williams began badly and got worse.

Despite her 17 grand slam titles and huge experience, it is not unusual for Williams to have days where nerves get the better of her and her movement deserts her.

One of the most painful defeats of her career came in Paris two years ago when she lost to Frenchwoman Virginie Razzano in the first round.

That was the moment she turned to coach Patrick Mouratoglou and began one of the most dominant spells of her career.

She has been particularly dominant on clay and last year finally won her second French Open crown 11 years after her first.

Williams was the overwhelming favourite to retain her title but, after winning the first game in cold and heavy conditions, she lost the next five.

Much of the credit must go to 20-year-old Muguruza, who struck the ball superbly and maintained her aggressive approach to ensure there was no way back for Williams.

The alarm bells really began to ring at the start of the second set when Muguruza broke the Williams serve for a third and then a fourth time to move into a 3-0 lead.

Williams, her shrieks growing ever louder, retrieved one break but then played a terrible game and looked close to tears as the match slipped away.

Muguruza was nerveless serving out the biggest win of her life, clinching victory on her first match point when Williams netted a backhand.

It completed a miserable day for the family after Venus had earlier lost to Anna Schmiedlova.

The sisters, who last lost on the same day at a slam at Wimbledon in 2011, had been expected to meet in the third round.