Norrie, who was looking for his successive ATP Tour title, simply couldn't stop a rampant Nadal in Acapulco.
The British number one, who won the Delray Beach event last week, lost Sunday's final 6-4 6-4 as the Spaniard's unbeaten start to 2022 continued.
Nadal, who is fresh from his record-breaking Australian Open triumph, claimed his fourth Mexican Open crown. His record this year is now 15-0 which marks his best ever start to a season.
It was the 35-year-old's 91st career title and he is now both the youngest and oldest champion in Acapulco, having first won as a teenager in 2005.
"It always has been a very special place," Nadal said on the ATP Tour website. "The energy that the people from Mexico bring to me is very unique.
"I went through some very difficult moments during the match that I was able to save, and then I took advantage when I had the chances.
"I'm very pleased. It was a very important title for me, so I can't be happier."
Although it ended in disappointment, it was another impressive week for Norrie, who is now ranked 12 in the world.
He beat world number four Stefanos Tsitsipas in the semi-finals, but was unable to stop Nadal, who won courtesy of a single break in either set.
Nadal's four titles - he has previously won in 2005, 2013 and 2020 - have him equal with David Ferrer and Thomas Muster as the most successful male players at Acapulco.