The Japanese star had not won a tournament since Memphis in 2016 and was hampered by a wrist injury the following year which forced a break from the 2018 tour.
He was runner-up in Brisbane in 2017 but went one better this year in a superb final.
Nishikori dominated his Russian rival throughout, despite a slight hiccup when one poor service game cost him the second set.
The second seed started slowly and went down 0-3 to the Russian.
But he recovered to break back and then seized the advantage at 3-3 when he broke Medvedev again, taking the first set in 42 minutes.
Nishikori was all over the Russian in the second set, his powerful and well-directed groundstrokes forcing Medvedev into errors.
Medvedev held on against Nishikori's multiple chances to break at 2-2 and 3-3 and took advantage of his opponent's poor service game to break ahead.
But any thought the Russian would take the momentum into the decider proved wrong as Nishikori stormed to a 5-1 lead, eventually wrapping up the final in just over two hours.
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