Nishikori has won twelve titles on the ATP Tour and was runner-up at the 2014 US Open,[4] making him the only man representing an Asian country to contest a major singles final.

A finalist in two USTA Pro Circuit events, Nishikori lost to Donald Young in Little Rock, Arkansas and Alex Bogomolov Jr. in Carson, California.

In October, Nishikori received a wildcard entry to the AIG Japan Open Tennis Championships in Tokyo, where he lost in the first round to Zack Fleishman.

In the final, Nishikori upset top seed James Blake in three sets to become the first Japanese man in nearly 16 years to win an ATP event.

On 30 August 2008, he became the first Japanese player to reach the round of 16 at the US Open in 71 years, when he beat fourth seed David Ferrer in five sets in what was considered one of the tournament's major upsets.

Nishikori opened the season in Chennai, where he upset two-time defending champion Marin Čilić in the first round, before falling in the quarterfinals to Janko Tipsarević.

[31] In the quarterfinals, he scored a rare upset over Australian Open champion Stan Wawrinka, who had thus far dominated their meetings to ensure that he would regain a top ten ranking.

Nishikori began the Asian Swing by entering the Malaysian Open as first seed and won for a third season title, beating Julien Benneteau in two sets.

Nishikori then played in the BNP Paribas Masters and reached the semifinals, defeating Tommy Robredo, Jo-Wilfried Tsonga and David Ferrer, each in three sets.

In February, Nishikori won his eighth singles title and became the first ever player to win the Memphis Open three times in a row, beating Kevin Anderson in straight sets in the final.

In the 2015 Miami Open, he defeated Mikhail Youzhny, Viktor Troicki and David Goffin all in straight sets losing only a total of 10 games to reach the quarterfinals.

Nishikori began his clay-court season at the 2015 Barcelona Open Banc Sabadell where he reached the final after beating Teymuraz Gabashvili, Santiago Giraldo, Roberto Bautista Agut and Martin Kližan.

Nishikori was given a tough draw at the 2015 Italian Open but managed to reach the quarterfinal after beating Jiří Veselý and Viktor Troicki, both in straight sets.

Nishikori started the Asian Fall by participating in his hometown tournament, Rakuten Japan Open, where he reached the semifinals, including victories over Borna Ćorić, Sam Querrey and Marin Čilić.

He began with victories over Philipp Kohlschreiber, Austin Krajicek and Guillermo García López before beating ninth-seeded Jo-Wilfried Tsonga to reach his third Australian Open quarterfinal, where he lost to Novak Djokovic.

Nishikori improved his feat by reaching the quarterfinal again in the Miami Open by beating Pierre-Hugues Herbert, Alexandr Dolgopolov and Roberto Bautista Agut in straight sets.

For the fifth consecutive year, Nishikori did not play in Monte Carlo and instead turned his focus to defending his Barcelona Open Banc Sabadell title.

He followed his good run by reaching the semifinals in the Mutua Madrid Open, beating Fabio Fognini, Richard Gasquet for the first time in seven meetings and rising teenage star Nick Kyrgios.

After beating Grigor Dimitrov and Stan Wawrinka in the quarterfinals and semifinals respectively, Nishikori then lost to Djokovic in straight sets in the finals, going 0–5 so far in the season against the Serb.

After an indifferent Asian swing season where he retired in his home tournament, the Rakuten Japan Open, Nishikori returned to action again in Basel, where he was the No.

At the 2018 Italian Open, he advanced past Feliciano López, third seed Grigor Dimitrov, and Philipp Kohlschreiber before losing to Novak Djokovic in the quarterfinals in three sets.

He defeated Maxime Janvier, Benoît Paire, and Gilles Simon before falling to seventh seed Dominic Thiem in the fourth round.

On January 25, 2022, Kei Nishikori announced that he will be undergoing arthroscopic surgery on his left hip and will be aiming to come back on tour in about six months.

[51] In June, after close to two years off the ATP Tour he returned at the Challenger 75 2023 Caribbean Open in Palmas Del Mar, Puerto Rico,[52] and won his first match against American Christian Langmo.

At his home tournament the 2024 Japan Open Tennis Championships, where he received a wildcard, he reached another quarterfinal defeating Marin Čilić[61] and Jordan Thompson,[62] before losing to sixth seed Holger Rune.

[64][65] In November 2024, Nishikori won his eighth ATP Challenger title at the HPP Open in Helsinki, Finland, defeating Luca Nardi in the final in three sets.

[67] He reached his first ATP Tour final in six years at the 2025 Hong Kong Open after the retirement of Shang Juncheng and returned to the top 100 in the rankings on 6 January 2025, for the first time since June 2022.

In 2015, the pair met in the semifinals of the 2015 Citi Open, with Nishikori coming back from a set down to prevail in three, and gain a place in his 15th career final.

During the round-robin stage of the Year-End 2016 ATP World Tour Finals, Cilic came from a set down to defeat Nishikori and ultimately prevail.

[citation needed] In the past, special versions of the Steam racquet have been sold by Wilson, exclusively in Japan, capitalizing on Nishikori's popularity in his home country.