Dejan Kulusevski, signed from Atalanta, scored on his debut in the 13th minute with only his sixth touch of the ball in a Juventus shirt before defender Leonardo Bonucci and Cristiano Ronaldo added two more in the last 15 minutes.
Former Milan and Juventus midfielder Pirlo had no senior coaching experience before he was surprisingly chosen to replace Maurizio Sarri in August, and only got his coaching badge last week.
Pirlo has cited Pep Guardiola, Carlo Ancelotti and Antonio Conte as his biggest influences but said that his style of football would be a mix of everything.
"I don't want to copy anyone, I have my own ideas and I will take my cue from the teams that impressed me," he said. "We haven't had much time because the boys have only been back for a week from their national team commitments."
"We saw a few things today and in the friendlies but it will take time to assimilate things. We are missing players but, with the ones we have, we will try to do the best we can."
His first match pitted him against one of Serie A's most experienced and wily characters, 68-year-old Claudio Ranieri.
Like Sunday's other Serie A matches, a smattering of fans watched the game after the Italian government authorised up to 1,000 spectators at matches for the first time since March.
As expected, Pirlo's side began with an aggressive high press and the pressure quickly paid off.
Ronaldo burst into the Sampdoria area and, although his run was blocked, the ball ran loose to Kulusevski who curled a precise low shot into the far corner.
Ronaldo also smacked his shot against the crossbar and then sidefooted wide following a neat exchange of passes as Juve dominated possession.
But, as expected from a Ranieri team, Sampdoria, who spent most of last season in the drop zone, were awkward opponents and it took Juventus until the last 15 minutes to finish them off.
Sampdoria failed to clear a corner, McKennie's effort was saved by Emil Audero, Bonucci snapped up the rebound and celebrated with his familiar gesture that suggests his critics should wash their mouths out.
Ten minutes later, Aaron Ramsey released Ronaldo and the Portuguese opened his account for the season by drilling his shot into the far corner.
"Today I didn't see the Samp I wanted to see, I'm very disappointed," Ranieri said. "We were too fearful. You can lose games but you have to try and play. Juventus played with hunger and my team didn't.
"We were lucky to get away with 3-0 because we could have conceded a lot more. We were timid, fearful and weak and I don't know why this happened."