The 26-year-old easily extended his unbeaten record to 17 wins from as many professional fights to retain his European super-bantamweight title at the Odyssey Arena on Saturday night.
The Jackal dominated the world title eliminator before delivering a brutal body shot in the sixth, with Parodi dropping to his knees before being counted out.
Frampton was on the front foot from the off, his left jab getting through early on and a couple of combinations troubling his French opponent in the opening round.
The Belfast favourite remained on top in rounds two and three of the bout, pushing his opponent back at every opportunity.
A solid left hand in the fourth sent Parodi staggering back and, with Frampton targeting a cut above the Frenchman's left eye, a couple of big right hands had him shaken.
But Parodi was proving to have plenty of courage, soaking up the punishment albeit without giving Frampton too much to think about.
The fierce left hook to the body thrown by Frampton at two minutes 59 seconds of the sixth was too powerful for the Frenchman, though, as he fell to his knees and was counted out.
Frampton had been out of the ring through injury, since famously beating Kiko Martinez in February. The Spanish boxer went to win the world super-bantamweight title.
After the fight Frampton told UTV he was ready to face the best super bantamweight boxers in the world.
"I'm coming for the top guys in the world. I've been in this game so long, I've made so many sacrifices and I'm not going to stop until I get to the top," he said.
Frampton also thanked the fans for their support.
"It's amazing, it's unbelievable. The support I get I could not have even dreamed about that when I first laced up a pair of gloves, even when I turned pro."
Promoter Barry McGuigan was full of praise for his protégé.
"This guy is a high quality fighter. The higher the pressure, the bigger the stage the better he will fight. He was impeccable tonight," he told UTV.
Meanwhile Eamonn O'Kane, from Dungiven, became the new IBF Inter-continental middleweight champion after defeating Kerry Hope.