Nagatomo officially signed with FC Tokyo in 2008, while at Meiji. But he made an appearance at J.League Cup as Special Designated Youth Player in 2007. Nagatomo made 84 appearances in his four years at FC Tokyo.
In July 2010, Nagatomo was signed on loan by the newly promoted Serie A side A.C. Cesena, where he played the first half of the season as Cesena's starting left back. Before moving to Italy, Nagatomo gave a speech to 25,000 supporters just after the match involving F.C. Tokyo and Vissel Kobe on 17 July 2010. After being signed on a permanent deal, Nagatomo was then sold to Internazionale.
Due to his impressive performances for both Cesena and Japan in the 2011 Asian Cup, he was fully signed by Cesena in January 2011. But before making any league appearances he was sent straight out on loan to Inter Milan in exchange for Davide Santon also on loan, becoming the first East Asian player to sign with Internazionale.
Nagatomo, wearing number 55, made his debut for Inter on 6 February 2011, replacing Wesley Sneijder in the Serie A match against Roma, which Inter won 5–3. In the following game, Nagatomo came on as a late substitute against Juventus, before starting in both of the following games against Fiorentina and Cagliari. Nagatomo has shown his versatility by playing right back against Sampdoria on 27 February 2011, and finishing the whole 90 minutes. On 6 March 2011, Nagatomo scored his first goal for Inter in the 5–2 trashing of Genoa on a Kharja assist with a swivel and a finish into the roof of the net.
On 15 March, to show solidarity with his home country in light of the catastrophic earthquake and tsunami which took place the previous week he paraded the Japanese flag (with the writing "You'll Never Walk Alone", a chant of his former team in Tokyo) around the pitch during a Champions League match against Bayern Munich. Inter had drawn German club side Schalke 04 in the quarter-finals of Champions League. Nagatomo, along with international teammate Atsuto Uchida who plays for Schalke became the second and third Japanese footballer to play in the quarter-finals of the UEFA Champions league (Keisuke Honda was the first playing for CSKA Moscow during 2009–10 season).
After the Serie A season was over, Inter Milan made an agreement with Cesena of making Yuto's move permanent in a cash plus player exchange deal. Nagatomo was valued at €10.95 million, however part of the fee was paid via half of the registration rights of Luca Garritano (€700,000) and Luca Caldirola (€2.5 million).
Nagatomo started his second Inter Milan season by playing 62 minutes in the opening Serie A match against Palermo, ended in a 4–3 away defeat. On 27 September 2011, Nagatomo provided an assist for Giampaolo Pazzini by nutmegging Aleksei Berezutski before driving the ball across goal during the 3–2 away win against CSKA Moscow in the second group stage match of Champions League. He scored his first goal of the season on 10 December 2011 during the 2–0 home win against Fiorentina in the matchday 15 of Serie A. He was again in the scoresheet three days later as he headed home an Ricky Álvarez cross in the 1–0 win against Genoa. In the last match of 2011 against Lecce at home, Nagatomo produced a "man of the match" performance by providing two assists in an eventual 4–1 win.
Nagatomo enjoyed his most productive season under Walter Mazzarri, scoring five goals, along with six assists during the 2013–14 season.
On 8 April 2016, Nagatomo agreed a contract extension with the club, signing until June 2019.
Nagatomo earned his first international cap for Japan on 24 May 2008 in a friendly against Ivory Coast. His first international goal was scored in a friendly against Syria held on 13 November 2008. Nagatomo was also a member of the Japan U-21 team for the 2008 Summer Olympics.
He was called up for the 2010 FIFA World Cup for Japan, and was named in Arsenal manager Arsène Wenger's best XI of the tournament.
Nagatomo was selected as part of the Japan squad for the 2011 AFC Asian Cup by coach Alberto Zaccheroni. He featured in every game Japan played in the competition and helped them defeat Australia in the final, thus earning his first international honour.
He was included in Alberto Zaccheroni's 23-man Japan squad for the 2013 FIFA Confederations Cup in which he featured in all three games Japan played before they were eliminated in the group stage.
Nagatomo was part of Japan's national squad to play in the 2014 World Cup in Brazil. He started in all three group matches but Japan was eliminated in the group stage.As of 17 September 2017
1Includes Emperor's Cup and Coppa Italia.
2Includes J. League Cup.
3Includes UEFA Champions League and UEFA Europa League.As of 19 June 2017
J. League Cup: 2009
Coppa Italia: 2010-11
AFC Asian Cup: 2011
Kirin Cup: 2011
Nagatomo is married to Japanese actress Airi Taira. The couple had maintained a long-distance relationship for several years as Taira was based in Japan. Nagatomo proposed to her on the San Siro pitch in February 2016 and they registered their marriage in January 2017.