Nadal, who lost his number world one ranking after his 14-match winning run on clay was snapped by Thiem in the Madrid Open quarter-finals last week, was back to his best as he wrapped up victory with a blistering forehand victor.
Nadal, a seven-time Rome champion, routed 31st-ranked Damir Dzumhur 6-1, 6-0.
It is the 13th time in his career Nadal has dropped only one game in a match, but he is still looking for his first "double bagel".
Fabio Fognini got the Foro Italico crowd fired up Wednesday with a 6-4, 1-6, 6-3 win over sixth-seeded Dominic Thiem in the second round of the Italian Open.
"Today was a positive day".
Nadal, a seven-time Rome champion, and four-time champion Novak Djokovic also advanced. "I don't know how many mistakes I did, but not much", said Nadal.
Also on the red clay of the Foro Italico, Albert Ramos-Vinolas rallied to beat eighth-seeded John Isner 6-7 (5), 7-6 (2), 7-6 (5).
"If you compare it to Madrid there were a lot of close matches I could have lost there too".
Also on the red clay of the Foro Italico, Kei Nishikori rallied to beat third-seeded Grigor Dimitrov 6-7 (4), 7-5, 6-4, and Juan Martin del Potro eliminated Greek qualifier Stefanos Tsitsipas 7-5, 6-3.
Pliskova racket rage Former world number one Karolina Pliskova was so angry she put a hole in the umpire's chair with her racket instead of shaking hands after losing to Greece's Maria Sakkari.
With the score at 6-3, 3-6, 5-5 and serving at 30-30, Pliskova had an overhead smash incorrectly called out, and after the umpire, Marta Mrozinska, could not find the ball mark the original call stood. "It was just him, he was very pumped playing at home". She could not hide her fury as she went on to lose the match 3-6, 6-3, 7-5.
On Halep's first match point, the 21st-ranked Osaka didn't even make a move for Halep's return of her second serve. "I'm more relaxed than in Madrid", said 26-year-old Halep.
If the Spaniard justifies his status as favourite by lifting the trophy, he will reclaim the world number one ranking from Roger Federer after slipping to second at the start of this week.
France's Caroline Garcia, a semi-finalist in Madrid last week, eased past Hungary's Timea Babos 6-3, 6-4, and will next face US Open champion Sloane Stephens.