The one hour 49 minute victory was Ferrer's fourth in Acapulco, and his first since the tournament switched from clay to hard court.
The Japanese star was easily overcome in the first set when Ferrer stormed to a 3-1 lead, and served out the set at love.
Nishikori was a harder prospect in the second despite allowing Ferrer to storm to a 3-0 lead. He fought back to four-all, but the Spaniard's break for 5-4 gave him his first chance to serve for the match. He broke back to five all, but Ferrer hung on and won the set.
Ferrer has now won two in a row after he defeated Fabio Fognini in the final in Rio De Janeiro last week. His record against Nishikori is now 4-7, after he previously lost five consecutive matches against him.
Despite this defeat, Nishikori will still rise to a career high of world number four when the ATP rankings are released next week.