Nadal, 21, took his record at the Monte Carlo Country Club to 21 wins in 22 matches with his only loss coming against Argentina's Guillermo Coria in the third round in 2003.
The Spaniard's third title in a row last year took him level with Ilie Nastase's three consecutive wins from 1971-1973.
"It's never easy to play Juan Carlos on clay so to beat him 6-4, 6-1 is a very good win for me," said Nadal who has now racked up 95 wins in 96 matches on clay since April 2005.
"I've had a great start beating Mario [Ancic] in the first round and now Juan Carlos.
|"It's never easy to play Juan Carlos on clay so to beat him 6-4, 6-1 is a very good win... "|
"The first claycourt tournament of the year is never easy especially this season because I played Davis Cup indoors in Germany last week. Then I had a few days at home in Mallorca before coming here to prepare for three days."
The triple French Open champion broke in the fourth game of the first set to lead 3-1 before 13th-seed Ferrero, twice a champion in 2002 and 2003, hit back in the seventh game.
However Nadal wrapped up the opening set with a vicious, deep forehand on his fourth set point.
Nadal was ahead at 2-0 in the second set with a punishing forehand return of a weak Ferrero second service and that soon became 4-0 with a well-placed drop shot.
The duo then exchanged breaks which left Nadal with a 5-1 lead which he converted into victory courtesy of a smooth forehand pass.
Ferrer and Federer through
Earlier Ferrer, who clinched his sixth career title in Valencia last weekend, reached his fourth successive Monte Carlo quarter-final by thrashing Serbia's Janko Tipsarevic 6-4, 6-0.
Ferrer's compatriot Nicolas Almagro was unable to join him in the last eight when he lost a marathon third round encounter to Russia's Igor Andreev.
Andreev won 7-5, 4-6, 6-4 but needed seven match points to secure his first place in the last eight and end the hopes of Almagro, one of the form players on clay this year.
The Spaniard went into Thursday's match boasting a 20-2 record on the surface in 2008 with two titles and a runners-up spot to Ferrer in Valencia.
Later, Roger Federer also moved into the quarters after defeating France's Gael Monfils 6-3, 6-4 in a far better performance than his second round match on Wednesday where he took three sets to overcome 137th ranked Spaniard Ruben Ramirez Hidalgo.