The top-seeded Nadal lost the opening set before recovering for a 4-6, 7-6 (6), 7-5 victory over the Frenchman.
"Was a very tough first round, as I say the other day," said Nadal, referring to his loss to Pouille in five sets at the 2016 U.S. Open. "He played well, I think. Very aggressive, he's serving well. For me was little bit difficult at the beginning. Then I started to play better, I think.
"But still, I didn't have the control of the match for almost all the time."
The third set was tied 5-5 before Nadal broke Pouille's service and then closed out the victory.
Pouille delivered 46 winners but also had 47 unforced errors.
Nadal next faces Russian Karen Khachanov, who posted a 6-4, 6-2 victory over wild-card Di Wu of China.
Wild-card Juan Martin del Potro advanced with a 7-6 (4), 6-4 victory over Pablo Cuevas in a battle of Argentinians. Another player from Argentina, Leonardo Mayer, also moved on with a 7-6 (6), 5-7, 6-4 victory over Italian Paolo Lorenzi.