After Nadal's 37-match winning streak on clay was ended last week by Djokovic in the Madrid Open final, the Spaniard fought back against Italian qualifier Paolo Lorenzi [ Images ] to advance 6-7, 6-4, 6-0 and maintain his record of never losing consecutive matches on the red dirt.
Nadal's nervy performance contrasted with that of second seed Djokovic who crushed Polish qualifier Lukasz Kubot [ Images ] 6-0, 6-3, and Federer, who overpowered Frenchman Jo-Wilfried Tsonga 6-4, 6-2.
Sixth seed David Ferrer was forced to pull out of his match against Marin Cilic [ Images ] through illness. There were also wins for Argentine Juan Ignacio Chela, ninth-seed Nicolas Almagro and 11th seed Mardy Fish [ Images ] while Feliciano Lopez [ Images ] will be Nadal's next opponent after overcoming Philipp Kohlschreiber 6-4, 3-6, 6-3.
"I played very badly," a non-plussed Nadal told reporters. "I was anxious, I felt slow and I was short all the time. I missed easy balls. I finished the match better and in the last game I played well.
"There is a big difference between Rome and Madrid. There you are playing at altitude and the ball is quicker. Losing the final also makes it more difficult because you arrive sadder. All these facts made it tough today."
Rome champion for five of the past six years, Nadal broke Lorenzi in the sixth game, but the Italian, ranked 148th in the world, refused to be intimidated by the strangely expressionless world number one and broke back before taking the set to a tiebreak.
Lorenzi chased everything down, forcing the Nadal machine to continually splutter and he sealed the set to send the usually sedate Italian crowd jumping to their feet.
The carnival atmosphere was quietened as Nadal broke serve in the first game of the second set but the gutsy 29-year-old was still mixing up his shots well and after the Spaniard took a tumble to stain his canary yellow shirt, Lorenzi broke back.
Lorenzi showed anxiety for the first time, though, at 4-4 and Nadal broke again before holding his serve to square the match.
In the deciding set, Nadal rediscovered the timing that had eluded him in the previous two to race to the finish against an exhausted opponent.
Djokovic, who claimed his sixth straight tournament victory in Madrid, was rarely made to sweat in the midday heat as he wrong-footed Kubot at will to take the first set to love.
But Kubot, ranked 141st in the world, did finally get on the board in the fourth game as he smartly altered his game plan to serve-volley, raising his arms as he walked back to his chair to the cheers of the Foro Italico crowd.
Djokovic, who will replace Nadal as world number one if he wins in Rome and the Spaniard fails to make the semi-finals, claimed his 33rd win in a row to close on John McEnroe's [ Images ] 42-match unbeaten start to 1984.
"It's a great way to start as you waste little energy. He was making a lot of enforced errors and coming to the net which didn't give me a lot of rhythm," said Djokovic, who next faces 14th-seed Stanislas Wawrinka.
Playing in the much cooler temperatures of the evening, Federer was rarely tested by Tsonga, breaking serve in the third game and twice more early in the second set.
"It was easier than I expected," the 16-times Grand Slam champion told reporters. "I played a clean match and I'm playing more aggressively which is working well for me."
Federer's next opponent will be Richard Gasquet.
"I'm excited to play Richard," the Swiss said. "We've had some great games in the past especially in Dubai [ Images ] recently. I'll expect a tougher match tomorrow."