Halep, a beaten finalist last year, was handed a tough second-round draw against Osaka, who defeated the top seed on her way to victory at Indian Wells earlier this year and saw off Victoria Azarenka in her opening match.
But the Romanian was in ruthless form on Thursday (AEST) as she tore through her opponent, winning 12 games in a row to complete a thrashing in just 59 minutes.
With the French Open just around the corner, Halep will see a potential triumph in Rome - the first of her career - as ideal preparation if she can continue in this vein for the rest of the week.
Osaka started brightly and held serve, before fighting back from 0-40 in the second game only to squander four break points as Halep clung on.
And with that, the 20-year-old's chance was gone. Halep breezed through the remainder of the first set, breaking three times as she set off on a stunning streak of dominance.
Osaka attempted to fight her way back in after falling 2-0 down in the second, but Halep twice saved break points and swiftly sealed victory.
She will face either Donna Vekic or Madison Keys in the third round on Friday.