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, AFP reported.
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.
Spain’s Roberto Bautista Agut overcame a mid-match scare to overcome Tomas Berdych 6-4, 3-6, 6-3 in the Qatar Open final for his ninth career title.
A day after outclassing world number one Novak Djokovic in the semifinals of the season-opening event, Bautista Agut came through another three-setter for his first title in Doha.
The world number 24 saved five out of six break points and converted two of his own in a tight final to see off Berdych, who was seeking his first ATP title since 2016, in a little under two hours.
“It’s been a fantastic week for me,” Bautista Agut, who endured some nervy moments in the decider, said. “Today it wasn’t easy to manage the emotions I had on court.”
The 30-year-old will look to carry the momentum forward to the Auckland Classic next week in his final warmup event before the Australian Open which begins in Melbourne on January 14.