But Nishikori, who had lost nine consecutive ATP finals over 52 tournaments in almost three years, broke the Russian player's serve on four consecutive points in the final game to clinch the match in just 2 hours, 6 minutes, at Pat Rafter Arena.
Nishikori has set his sights on returning to the world's top five after falling to 39 last April due to a wrist injury at the end of 2017 that forced him to take a break from the tour.
Kei Nishikori says he would've arrived in Melbourne happy even if he had lost a tenth-straight ATP final on Sunday.
Medvedev defeated Raonic in Tokyo last October en route to his first ATP 500 title and he emerged as the victor today as well, overcoming the opening set deficit and all eight break points he faced to leave the big server behind in sets two and three and set Tsonga clash for the place in the final.
The fourth-seeded Russian kept his nerve on Friday to defeat 2016 champion and fifth seed Milos Raonic of Canada 6-7 (2), 6-3, 6-4 in two hours and nine minutes at the Brisbane International.
"Despite the many chances that he had, I managed to hold my serves so I'm happy about it and the win... to see that what I have been working on in the off-season works in Brisbane is already a good sign".
"I feel nearly home there, so I hope I can do well, better than a quarter-final".
Hoping to extend his first-tournament appearance, Medvedev broke Raonic's serve at the beginning of the second set and sent on to draw level.
"I play such a physical game I'm trying to save my legs as much as I can".
The Russian, who stands at 1.98 metres, was able to withstand the huge serving of Tsonga and out-hit him from the baseline.
"I've never had a week like this to start the season, so it gives me a lot of confidence".
"I didn't do anything wrong".
The Spain-based teenager lamented a handful of missed opportunities that came amid a barrage of Tsonga winners.