The Spanish world number nine's triumph put him level with Austrian Thomas Muster with four Mexican titles having also won the tournament three times from 2010-2012 on clay.
It was Ferrer’s third title this year after Doha and last week’s win in Rio de Janeiro and 24th of his career, ending a run of five defeats to the Japanese top seed.
Nishikori now leads Ferrer 7-4 in their meetings.
"I played very aggressive, without mistakes. I'm very happy. To win here a fourth time is a dream," Ferrer was quoted as saying on the ATP website.
"In important moments, he made more mistakes and I took my chances. I feel very confident with my tennis now. I've won three tournaments this year and we've only began the season."
Ferrer was dominant almost throughout the match with Nishokori, set to rise to world number four after reaching the final, on the back foot and 3-0 down in the second set after twice being broken by the Spaniard.
However, the 2014 U.S. Open finalist fought back to 4-4 then 5-5 as the players exchanged further breaks before Ferrer clinched it in one hour and 49 minutes.
Swiss Timea Bacsinszky won the women’s crown beating Caroline Garcia of France 6-3, 6-0 in the final.
Image: David Ferrer
Photograph: Matthew Stockman/Getty Images
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