However, fellow seeds Tomas Berdych and Jo-Wilfried Tsonga were given stiff tests.
Fifth seed Nadal, who is looking for back-to-back titles after triumphing in Barcelona two weeks ago, needed one hour and 26 minutes to wrap up his 6-3 6-4 victory over determined Frenchman Benoit Paire.
Nadal, whose hopes of claiming another title ahead of the French Open were boosted by Tuesday's shock departure of world number one Novak Djokovic, paid tribute to his beaten foe today.
"That's an important victory today," he said on the ATP Tour website. "Each match in this kind of tournament is very demanding from the first round.
"He was a very uncomfortable opponent. He makes you play quite badly. He doesn't give you any rhythm. He has one of the best backhands in the circuit, without any doubt."
Compatriot Ferrer bounced back from his setback in the Barcelona Open by swatting aside Denis Istomin.
The world number four was defeated by Russian qualifier Dmitry Tursunov at the Real Club de Tenis Barcelona in the second round two weeks ago but he showed no ill-effects of the loss with a 7-5 6-2 win today against his Uzbekistan opponent.
Sixth seed Berdych became the second player this week - after Andy Murray yesterday - to win his 400th career match although he was pushed all the way by Poland's Jerzy Janowicz.
The Czech faced nine break points in the match but managed to save eight of them as he came through 6-7 (3/7) 6-3 6-2.
Tsonga, seeded seventh, also found the going tough but the Frenchman managed to just edge out Dutch qualifier Robin Haase 7-6 (7/5) 7-6 (7/2) in one hour and 46 minutes.
Eleventh seed Nicolas Almagro was the day's biggest casualty, the Spaniard going down 7-6 (7/4) 4-6 6-2 against Russia's Mikhail Youzhny although there were no such worries for 14th seed Kei Nishikori, who was a 7-5 6-2 winner over Viktor Troicki.
Tommy Haas overcame Spanish wild card Tommy Robredo 6-3 7-5, Kevin Anderson saw off Juan Monaco 7-6 (7/5) 3-6 6-4 and Stanislas Wawrinka eased past Santiago Giraldo 6-3 6-3.
In the women's draw, Victoria Azarenka suffered her first defeat of the year following, against Ekaterina Makarova.
All looked to be going to plan for the Australian Open champion, who was playing her second match since an ankle injury, when she won the first set but her Russian opponent rallied to a 1-6 6-2 6-3 victory, which included winning the final five games of the match.
"I have to give Ekaterina credit - she played really well," Azarenka, who had won all 18 of her matches this year prior to today, said on the WTA Tour website. "I felt like I had a lot of chances, I just didn't take them.
"I put myself down a little bit. I didn't play for a long time. I haven't lost a match for a long time. But this happens - it was going to happen sooner or later anyway.
"I just want to do better in the next tournament and kind of pick it up."
Laura Robson failed to build on her win over world number four Agnieszka Radwanska as 16th seed Ana Ivanovic claimed a 5-7 6-2 7-6 (7/5) win in two hours and 13 minutes to book a quarter-final match against Angelique Kerber, who saw off 2009 French Open champion Svetlana Kuznetsova 3-6 6-4 7-5 in the third round.
There were also victories for Varvara Lepchenko, Kaia Kanepi and Maria Kirilenko, all of whom qualified for the last 16.