Pogacar, 22, became the youngest Tour de France champion since 1904 when he won the pandemic-delayed 2020 race last September.
Pogacar finished the 21-stage race five minutes, 20 seconds ahead of Denmark's Jonas Vingegaard, with Ecuador's Richard Carapaz another minute, 43 seconds behind in third place.
Belgium's Wout van Aert took the final stage win, giving him three total in the event and denying Mark Cavendish a record-breaking 35th stage win in a sprint to the finish.
"This Tour has just been amazing, it's such a rollercoaster," said Van Aert. "To finish with a win like this, is beyond expectations."