court, was ousted 3-6, 6-4, 6-3 by big-serving South African Kevin Anderson in the second round at the Indian Wells Tennis Garden.
Four-times champion Federer, however, wasted little time in pounding Uzbekistan's Denis Istomin 6-2, 6-3 with a ruthless display of seemingly effortless movement and razor sharp shot-making.
"It's nice to be back as defending champion and to start so strong today," Swiss maestro Federer said courtside after sealing victory in just under an hour on his second match point.
"Denis Istomin can play really well. I came out and played exceptionally well so I am happy."
Federer, who beat American John Isner 7-6, 6-3 in last year's final at Indian Wells, was in peerless form on Saturday, blending a series of crunching groundstrokes with his typically dominant net play to break Istomin's serve twice in each set.
Earlier, fourth-seeded Ferrer was overpowered by his towering opponent in the final set as Anderson booked his place in the third round after a contest lasting just under two hours.
Serving for the match in dazzling sunshine, Anderson earned his first win against the Spaniard in two career meetings when Ferrer dumped a backhand service return into the net.
The six-foot eight-inch (2.03 metre) South African, ranked 37th, clinched both fists in jubilant celebration before walking to the net to shake hands with his opponent.
"That was fantastic," smiled Anderson, who had surgery on his right elbow in late January. "Beating a top-five-in-the-world player is always a great feeling, especially against somebody like David, who doesn't go away."
Anderson, who broke Ferrer's serve once in the second set and twice in the third, will next face Finland's Jarkko Nieminen, who crushed Spaniard Fernando Verdasco 6-1, 6-0 earlier in the day.
Ferrer was frustrated after squandering two break points on Anderson's serve in the ninth game of the second set.
"I had my chance at 4-4 ... but he played good in important moments," Ferrer said. "He played more aggressive, more consistent than me.
"In the third set I was a little bit tired and he was better than me. Of course I am disappointed because I lost my first match, but this is tennis. It's impossible to win always."
In other matches, twice former champion Lleyton Hewitt of Australia upset 15th-seeded Isner 6-7, 6-3, 6-4 while Swiss Stanislas Wawrinka came from a set down to beat American Wayne Odesnik 3-6, 6-2, 6-1.
Later on Saturday, Spaniard Rafa Nadal, sidelined for seven months last year by a left knee injury, faces American Ryan Harrison.