Klitschko sent the Bulgarian flying back with a huge left punch to his jaw, leaving him sprawled on the canvas and giving referee Tony Weeks no option but to end the bout.
Klitschko, taller with a longer reach, dominated from the start and had the IBF's mandatory challenger down twice in the opening round, first with a left jab. Pulev stood up again, stuck out his tongue and stood on one leg to show he was OK, but the Ukrainian knocked him down again straight away.
Klitschko dropped him to the canvas again in the third, which Pulev did well to finish with a bloody left eye.
Just when the challenger seemed to be improving, Klitschko finished the bout abruptly, 2 minutes, 11 seconds into the fifth.
Klitschko recorded his 54th KO in 63 wins, with three defeats, and he dedicated his latest victory to the Ukrainian people, "who are going through tough times."
"To Pulev's fans I want to say, you have to be sporting, Pulev fought a good fight," the 38-year-old said. "It was hard to work, the left jab. Pulev prepared well."
Pulev, who dropped to 20-1 (11 KOs), said Klitschko was "lucky."
"Wladimir is a really good opponent, but he was lucky. I want a rematch. I'll win the next time," Pulev said. "There's luck in boxing. He's a good boxer but he's unsporting. There were a lot of tricks."
Pulev was warned more than once by Weeks for punching to the back of Klitschko's head.