Garbine Muguruza was the latest high-profile player to make an early exit at the Madrid Open on Monday, but Victoria Azarenka extended her winning run to 16 matches by beating Alize Cornet.
Agnieszka Radwanska and Angelique Kerber - the top two seeds - suffered first-round exits on Sunday and third seed Muguruza was beaten 5-7 7-6 (7-4) 6-3 by Irina-Camelia Begu in round two on home soil a day later.
Azarenka is eyeing a third consecutive title, having being crowned champion at Indian Wells and in the Miami Open, and the world number five moved a step closer by seeing off Cornet 6-3 6-2.
Defending champion Petra Kvitova was a 6-3 6-3 winner against qualifier Elena Vesnina, while Elina Svitolina and Ana Ivanovic were among the other seeds to crash out on the clay.
SEEDS CONTINUE TO FALL
Muguruza was the highest seed remaining in the tournament following defeats for Radwanska and Kerber, but the world number four also suffered a shock defeat.
Last year's Wimbledon runner-up recovered from 3-0 down to win the first set, but lost her way in the second and was unable to serve out the match to allow Romanian Begu to pull off an upset.
Daria Gavrilova accounted for Svitolina (12) with a 6-2 7-6 (7-4) victory, while Christine McHale dumped out 13th seed Karolina Pliskova 7-6 (7-3) 6-4 in the second round.
Sloane Stephens (16) also failed to cash in on defeats for Radwanska and Kerber as the American was beaten 6-2 6-3 by qualifier Patricia Maria Tig before Ivanovic was ousted.
AZARENKA TAKING ON ALL COMERS
The in-form Azarenka had won all four matches against Cornet and maintained that perfect record with another impressive display.
Former world number one Azarenka did not have things all her own way, but conjured up some powerful returns to take charge of the match and saved seven break points to thwart Cornet.
Azarenka said: "I feel that this year is going to be all about making progress and trying to improve, making errors but still improving."
DEBUTANT CHIRICO OUSTS IVANOVIC
Louisa Chirico had never featured in the main draw in Madrid before now, but the American qualifier fought back to dump out 2008 French Open champion Ivanovic.
World number 130 Chirico showed great character to prevail 5-7 6-1 6-3 on a warm day in Madrid after Ivanovic lost her grip on the second-round match.
Ivanovic led 2-0 in the final set, but Chirico refused to lie down and will now face Azarenka in the third round on the red stuff.
HALEP, STOSUR IN ACTION
Romanian sixth seed Simona Halep - runner-up in Madrid in 2014 - will seek to reach the third round when she faces Karin Knapp on Tuesday. As for Samantha Stosur, the 2006 French Open champion takes on 11th seed Lucie Safarova.