The 32-year-old admitted in a press conference to preview the ATP 500 event that he had been struggling with his hand which meant he could not train.
The 17-time Grand Slam champion put the issue down to a “bad movement” made while he was practicing in Cozumel, admitting he had not enjoyed “the best feelings” ahead of his opening match.
But Nadal saw off the challenge of world No 76 Zverev – the older brother of Alexander Zverev – in one hour and 20 minutes with a routine 6-3, 6-3 win.
The top seed in Acapulco, Nadal has reached the final on all of his last three trips to the tournament and the Spaniard was a class above on Cancha Central.
The world No 2 sets up an intriguing second-round clash with Nick Kyrgios, who downed Italy’s Andreas Seppi 6-3, 7-5.
Speaking to ATP World Tour after seeing off Zverev, Nadal said: “[I’m] Happy for the victory of course.
“[It’s] A good start for me, never easy against Mischa. And especially after a while without competing.
“I had some problems in the hand last couple of days without practicing much so it’s an important victory for me.
“Now [I] just [want to] enjoy these few hours and try to be ready for tomorrow.”
This was Nadal’s first return to the court since losing the Australian Open final to Novak Djokovic last month.
And he was treated to a rousing reception from the crowd in Mexico.
On the fans, he added: “It’s fantastic, it’s always the same here in Acapulco.
“A lot of love from the crowd, big support and I feel it’s a bit like home.”
Nadal has an excellent 15-1 record at the event, which he was twice but not since it changed from being played on clay courts to hard courts five years ago.
His only ever loss came to Sam Querrey in the 2017 final.
Elsewhere on the opening day, Second seed Alexander Zverev won 6-3, 6-3 against Australia’s Alexei Popyrin.
Nadal cannot mean German Zverev until the final.