He made his official CD debut as part of boyband NEWS in 2004 under the Johnny's Entertainment label and later debuted as a solo artist in 2006 with the hit single "Daite Senorita". He released his first solo album in 2011 and left NEWS in the same year. His first post-NEWS single, Love, Texas(愛, テキサス) was released under Warner Music Japan in 2012. Warner Music Japan only as his label for music release, his agency and career management remain under Johnny's Entertainment and Johnny & Associates.
Yamashita graduated from Horikoshi Gakuen's performing arts course for high school students in 2004. At Horikoshi, he shared a classroom with celebrities such as Koki Tanaka, Koike Teppei, and Yu Shirota. After graduating from high school, Yamashita was accepted into Meiji University's School of Commerce. He graduated with a Commerce degree (major in marketing) in autumn 2008, a semester late.
Yamashita joined Johnny's and Association in 1996. He was 11 years old that time. He started as trainee or in Johnny's called "Johnny's Junior". Johnny's Juniors appeared on music shows as their senior backdancers and they also regular appearance on NHK "The Shounen Club", a music show made for Johnny's Juniors. In few years, Yamashita popularity rise and he was one of most popular amongs juniors in his generation. After Takizawa Hideaki debuted as duo grup Tackey & Tsubasa in 2003, Yamashita was appointed as Johnny's Junior leader.
Yamashita made his acting debut in NHK's Shonentachi in 1998 and getting more attention after drama series Ikebukuro West Gate Park in 2000. From then on, he began his acting career, started from small roles to more important roles.
In September 2003, 7 years after joining the agency, Yamashita was one of the Johnny's Juniors chosen to be part of the boyband NEWS and he subsequently formally debuted as part of NEWS on May 12, 2004. Yamashita was often referred to as the leader of NEWS in media but members of the group, including Yamashita himself, have stated at times that he was not the de facto leader.
He released the single Seishun Amigo with Kazuya Kamenashi in November 2005. The single was the soundtrack for the drama Nobuta wo Produce starring Kamenashi and Yamashita, and topped the Oricon yearly charts in 2005.Seishun Amigo eventually sold over 1.5 million copies and is Yamashita's best-selling single to date.
His biggest break as an actor came in 2006 when he landed the titular role in the hit television drama Kurosagi. He subsequently made his widescreen debut with the Kurosagi film sequel Eiga: Kurosagi in 2008. Yamashita also made his debut as a solo artist with the Kurosagi soundtrack Daite Senorita which went on to sell over 800,000 copies. He followed that up in 2007 and 2008 with turns as time-traveler Iwase Ken in the award-winning romantic comedy Proposal Daisakusen and flight doctor-in-training Aizawa Kousaku in the medical drama Code Blue.Proposal Daisakusen remains one of his most notable works and in 2013, his character Ken's trademark line "Hallelujah chance! (ハレルヤチャンス!)" was selected by Oricon Monitor Research members as one of the most memorable signature phrases in Japanese drama history.
Industry watchdog Nikkei Entertainment placed him at the top of their annual ranking of under-30 japanese celebrities in 2008 due to his achievements in multiple entertainment fields that year. Following his work in the 2009 romance serial Buzzer Beat, Nikkei christened him the 'twenty-something ratings man', singling him out as one of the few young actors who could successfully lead romance dramas and possessed a stable ratings record despite the declining drama industry. The year 2009 also marked Yamashita's return to solo music activities with the release of his second solo single Loveless and the Tomohisa Yamashita: First Solo ~Short But Sweet~ concerts.
Yamashita reprised his role as Aizawa Kousaku in the winter 2010 tv series Code Blue 2. Days after Code Blue 2 was wrapped up, Yamashita began filming for the live-action film adaptation of Ashita no Joe. Code Blue 2 and Buzzer Beat aired in Fuji TV's prestigious getsuku (Monday 9 p.m.) time-slot in Japan, making Yamashita the first person to have starred in two getsukus with only a single drama season in between. That same year, he released his third solo single One in a Million which debuted atop the Oricon charts. This was followed by the releases of the single Hadakanbo and his first solo album Supergood, Superbad in January 2011. His first solo tour, "Supergood, Superbad: Asia Tour 2011" kicked off on January 29, 2011 in Hong Kong.
On October 7, 2011, Johnny & Associates announced that Yamashita and Ryo Nishikido were no longer members of NEWS, and Yamashita would henceforth be concentrating on his solo projects. Yamashita later published a message through the Johnny's web (Jweb) subscription service stating that this was a decision taken after much consideration on his part.
From January to March 2012, NTV aired Yamashita Tomohisa Route 66: Tatta Hitori no America(山下智久・ルート６６～たったひとりのアメリカ), a travel documentary chronicling Yamashita's cross-country trip across the historic Route 66.
After a two-year absence, Yamashita returned to the small screen with the winter 2012 drama serial Saikō no Jinsei no Owarikata: Ending Planner where he portrayed the role of Ihara Masato, the reluctant heir to a funeral parlor. He also co-starred with Shingo Katori in the autumn 2012 detective series Monsters. A chance meeting at a Lady Gaga concert before production began on Monsters led Katori and Yamashita to co-author the drama theme and they later formed a temporary unit named The Monsters to release the theme as a single. The Monsters came together again in 2013 to co-author the track PAri-PArA for Yamashita's 3rd album A NUDE.
As of 2013, all 3 studio albums released by Yamashita received the Gold certification for shipment of 100,000 copies by RIAJ (Recording Industry Association of Japan).
Yamashita started his new job of variety host by co-hosting Fuji TV's primetime Japanese variety showShogeki! Sansedai Hikaku TV: Generation Tengoku(衝撃!3世代比較TV ジェネレーション天国) from January 28, 2013 until its last episode on March 10, 2014. From April 20, 2014, Yamashita started hosting a new late-night variety show titled Otona no Kiss Eigo. Later in 2015 the staffs put his name on the title show and changed to YamaPi no Kiss Eigo (with new timeslot and format games and pranks involving English) 
In April 2014, it was announced that Yamashita had been cast as the male lead in the live action film adaption of the manga, Kinkyori Ren'ai (近キョリ恋愛, "Close-range Love"), in which he would play a new English teacher at a high school who becomes the object of affection for one of his students, Kururugi Uni (played by new actress Komatsu Nana). "近キョリ恋愛" topped the Japan box office for 3 consecutive weeks, earning total 1.17 billion yen. It was the only movie with less than 200 screens (179 screens) which managed to earn over 1 billion yen in 2014.
In October 2014, Yamashita released his 4th studio album titled "YOU", following the limited release of his first dance mini album titled "Asobi" in August, which was his first attempt at having only dance music in a mini album.
In February 2015, it was announced that Yamashita will be starring in TBS' spring 2015 drama, "アルジャーノンに花束を" (Algernon ni Hanataba wo). The drama will be an adaptation of the Daniel Keyes novel, Flowers for Algernon
In May 2015, Yamashita started his new regular radio program titled “SOUND TRIPPER“ after his old radio program "CROSS SPACE" (2012-2015) ended few weeks before. Based from the new show’s title, SOUND TRIPPER, the interFM show will let you enjoy chart-topping songs from US and UK charts of that year. Yamapi’s “SOUND TRIPPER” broadcast 5 days a week, from 8:05-8:10 in the morning.
Later in October 2015 for the fall drama, Yamashita announced to star in Fuji TV getsuku 9 drama 'From Five to Nine/5-ji Kara 9-ji Made' an adaptation from manga with same title. He paired with popular actress, Ishihara Satomi.
January 2016, Yamashita's music back to surface after 2 years hiatus from 2014. On January 27, he finally release his first best album "YAMA-P" consist some hit songs and his original song "Dreamer". The album easily top #1 oricon chart weekly 
May 2016, Yamashita along with Ito Hideaki, Shun Oguri, Yamada Takayuki, Takei Emi starred ont the live action movie of popular manga and anime "TerraFormars" directed by Miike Takashi.
In early 2016, It was also announced that Yamashita joined a Chinese movie production. The movie title "ReBorn" (not official) which he play as important supporting actor and his first time as villain character. He is co-starred with other popular Asian actors such as Hangeng (Chinese actor) and Rydian Vaughan (Taiwanese actor). They went to some countries in Asia for filming (Hong Kong, Shang Hai, Malaysia etc.). Detail info and release date of the movie still not yet announce, probably 2017 or 2018.
From June to August 2016, Yamashita back with his long-awaited nationwide concert tour "Yamashita Tomohisa~The Best Live Tour 2016 Future Fantasy" (his last concert Tour "A NUDE" was in 2013). With great feedback and high demand from his fans, he did 2 days more additional concert shows for Future Fantasy Yoyogi (Tokyo) on December.