The second-seeded Spaniard, who has only lost one match at Roland Garros since his debut in 2005, produced his usual awe-inspiring mix of power and pace to dismiss the world number 111 in just under two hours on Court Philippe Chatrier.
Nadal raced to a 6-2 4-0 lead but Bolelli pulled a break back when his opponent double-faulted but that was as good as it got for the Italian.
The former world number one completely dominated an error-prone Bolelli, who summed up his ordeal in three words: "Today, no chance."
Nadal, who will next face Uzbekistan's
Nadal, meanwhile, admitted he had mixed feelings about centre court at Roland Garros, despite having won six titles there.
"I'm not the right player to say I don't like that court. That's the first thing," he replied when asked he if he found the court tricky to play on.
"But I know an opinion that it's true it's not an easy court. Difficult court to play. A lot of wind around. The conditions can be very difficult to play.
"Because a lot of days in the outside court, the wind is almost zero, and you go to the centre (court) and you feel the wind.
"So it's a little bit strange thing, but that happens."
Lacko tried to fight back towards the end, saving three breakpoints to hold serve for 4-1 in the third set, but it was already too late and he surrendered serve to the claycourt specialist in the seventh game to go out.
Ferrer, a quarter-finalist twice in Paris and the sixth seed, will face Frenchman
The eighth seed recovered his concentration to defeat American
"He was playing out of his mind, hitting winners from everywhere, playing a little bit outside the situation how you normally should play on clay," Tipsarevic said.
"All credit to him. Everything was going in. I'm happy that I managed to stay positive, stay quiet, not really talk too much when somebody is killing me on the court like he did in the first set."
Britain's fourth seed Andy Murray also went through in straight sets, ousting Japan's Roland Garros debutant Tatsuma Ito 6-1 7-5 6-0.
The Scot will next face Finn