The UAE Team Emirates rider had been in the leader's pink jersey since winning stage two, the first of his six stage successes, and finished Sunday's ceremonial 125-km flat run safely in the bunch as Tim Merlier won the stage.
"I am speechless, it's hard to describe this moment, it's amazing," Pogacar said.
"A lot of nice memories for sure, in a while I will see which one was the best moment but I think in general it was a really beautiful Giro."
Merlier (Soudal–Quick-Step) outsprinted Italy's Jonathan Milan (Lidl-Trek) as the Belgian won his third stage. Milan had made his way back to the front for the bunch sprint after crashing on the last lap around the Eternal City.
"For the people, it's a really big win, but for myself, it feels a bit strange because everybody was already on the plane yesterday, drinking beer and everything," Merlier said.
"Today we need to race. The first part easy, then it was full gas. For me, this kind of race is a bit special, for sprinters a really nice victory."
Milan, winner of three stages, had the consolation of winning the points classification, ahead of Australian Kaden Groves (Alpecin-Deceuninck) who finished third in the final stage.
Pogacar finished nine minutes and 56 seconds ahead of Colombia's Daniel Martinez (BORA-Hansgrohe), with last year's runner-up Geraint Thomas of Wales (Ineos Grenadiers) a further 28 seconds behind in third in the overall standings.
He adds the Giro title to his two Tour de France triumphs in 2020 and 2021, and did it in style, proving exactly why he had been the pre-race favourite as nobody came even close to challenging once Pogacar laid down an early marker on day two.
Last year's winner and fellow Slovenian Primoz Roglic was absent from the race along with Remco Evenepoel and Jonas Vingegaard, but nothing can take away from Pogacar's domination in Italy, and he will now aim for the Tour de France.
Pogacar really took control on stage seven by winning the individual time trial ahead of Filippo Ganna, stretching his lead to over two and a half minutes, and followed that by winning the next stage.
Ganna gained revenge in the next time trial but Pogacar still extended the gap to his rivals when finishing second, and by stage 15 it was all but over when the Slovenian won his fourth stage and put an extra three minutes between himself and Thomas.
Pogacar won the weather-hit next stage and showed no mercy on the penultimate day when going solo to take his sixth stage to cement his grip on the maglia rosa, with an overall lead not seen in almost 60 years at the Giro.
The Slovenian also won the mountains classification and Pogacar could relax on the final day and enjoy his first ride around the streets of the Italian capital safe in the knowledge he was the Giro winner without a shadow of a doubt.
He celebrated after the finishing line with his team, all wearing special pink trimmed jerseys for the final day, and later lifted the trophy in the shadow of Rome's Colosseum, with the Slovenian anthem ringing out for the second successive year.
"The pink jersey is really special, a crazy experience, and the whole defence was unbelievably good, so yeah, it was crazy," Pogacar said.
