Playing his opening match in the round of 32 in the French capital, the German accumulated errors to tamely exit the tournament against the 24-year-old Italian.
Former world number five Musetti became the fifth man to defeat a player in his opening match as the world number one.
But Zverev insisted that the pressure of being the top-ranked player was not the cause of his poor performance.
"Stress, I don't know if stress. I was a bit annoyed, to be honest," he told reporters.
"The last couple of days, because, you know, achieving the world No. 1 status is something that I think every player dreams of.
"But then I feel like I'm the only world No. 1 in tennis history that has to explain why it's okay for me to be world No. 1, which I find quite difficult, because I think I deserve to be where I am, even though I lost today."
In the opening set, both players staved off break points in consecutive games midway through the frame, but it always looked destined to be decided by a tie-break.
The Hamburg native got ahead 5-2 in the breaker, but Musetti rallied to string together a run of five consecutive points to take a one-set lead, sealing it with a huge serve out wide to Zverev's backhand.
The Italian was now brimming with confidence, and after failing to convert a break opportunity in the first game of the second set, he made no mistake two games later as he capitalised on an error-strewn display from Zverev.
Musetti continued to deploy a sliced backhand to devastating effect as unforced errors mounted on the 2024 Paris Masters champion's side of the net, culminating in a second break which allowed the Italian to serve for the match.
The world number 24 did just that, sealing his progress to the last 16 to love against a dejected Zverev.
"Personally, I felt that today, I was enjoying (it), even when I was losing in the tie-break, I kept that in mind to enjoy, you know, the beauty of this sport," Musetti said on-court.
"It paid off, I'm really, really happy."
Zverev, himself, recognised that the Tuscan was a level above him on the day.
"To simplify it, he played really good, and I played really bad," the 29-year-old said.
"I think this was not a very good match from me, I think it might be one of the worst in the last couple of months."
