The first two games produced some brilliant tennis, with Nishikori pushing Ferrer hard on his serve in the opener.
The Spaniard found big serves when he needed to, denying the Japanese the break to register the first game on the scoreboard.
After a comfortable hold, Nishikori again went on the offensive as Ferrer served. He worked his opponent across the court and earned more break points.
However, Ferrer hung on in typical fashion, before taking his own opportunity when it came in the next game.
The fifth seed managed to hold onto his serve to take the first set 6-2.
Nishikori was feeling the effects of tendinitis in his knee, which was heavily bandaged. His mobility was clearly affected, as Ferrer raced into a 5-0 lead in the blink of an eye.
The 23-year-old did manage to avoid a second-set whitewash, but could not stop Ferrer from eventually edging further clear.
A rejuvenated Nishikori drew first blood in the third set as he looked for an unlikely route back into the match, but Ferrer struck back immediately to even the scoreboard.
The pair exchanged breaks once more, before Ferrer's dogged nature saw him claim the fateful break after a 10-minute game to take a 5-4 lead.
There were no finishing-line jitters from the 30-year-old as he comfortably closed out a 6-2 6-1 6-4 victory.