[2] Yamashita joined the Japanese talent agency Johnny & Associates as a trainee in 1996 and made his small acting debut for NHK's Shonentachi (1998).

Yamashita is widely known for his many popular dramas such as Nobuta wo Produce (2005), Kurosagi (2006), Operation Love (2007), Buzzer Beat (2009), Code Blue, and 5→9 From Five to Nine (2015).

Yamashita became motivated to send in his application to the talent agency Johnny & Associates after watching one of Takizawa Hideaki's dramas and aspiring to appear on television like him.

[8][9][10] Yamashita also made his debut as a solo artist with the Kurosagi soundtrack Daite Senorita which went on to sell over 800,000 copies.

[8][11][12] He followed that up in 2007 and 2008 with roles 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.

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.

[17] Then, after a two-year absence, Yamashita returned to the small screen with the 2012 winter drama Saikō no Jinsei no Owarikata: Ending Planner where he portrayed the role of Ihara Masato, the reluctant heir to a funeral parlor.

[2] 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 new format games involving speaking English.

The radio program was aired from 2015 to early 2017[21] In 2014, Yamashita was 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 plays an English teacher at a high school who becomes the object of affection of his student Kururugi Uni, played by Komatsu Nana.

The first was the TBS spring 2015 drama, "アルジャーノンに花束を" Algernon ni Hanataba wo (2015), an adaptation of the Daniel Keyes novel, Flowers for Algernon.,[25] in which he played the lead character.

In fall, he starred in the romance-comedy drama 5-ji Kara 9-ji Made: Watashi ni Koi Shita Obōsan alongside actress Satomi Ishihara.

The movie was released on August 3, 2018 in China and January 25, 2019 in Japan[27] In April 2017, Yamashita and Kamenashi Kazuya starred together again in the spring drama "Boku, Unmei no Hito desu ~ I'm your Destiny" .

Code Blue is the fifth domestic live-action movie to achieve this as well as the first in fifteen years to do so; the previous film to accomplish this was Bayside Shakedown 2 in 2003.

Most notably, he starred as a lead actor in the psychological thriller series The Head, an international production of THE MEDIAPRO STUDIO and HBO Asia.

[29] In 2022, Yamashita appeared as Akira in HBO Max's Tokyo Vice alongside Ken Watanabe and Hideaki Itō.

[30][31] In 2023, Yamashita starred as brilliant oenologist Issei Tomine in the live-action adaptation of legendary manga Drops of God for Hulu Japan and Apple TV+.

After Takizawa Hideaki debuted as duo group Tackey & Tsubasa in 2003, Yamashita was appointed as Johnny's Junior leader.

In September 2003, 7 years after joining the agency, Yamashita was one of the Johnny's Juniors chosen to be part of the idol group NEWS and he subsequently formally debuted on May 12, 2004.

The single was the soundtrack for the drama Nobuta wo Produce, starring Kamenashi and Yamashita, and it topped the Oricon yearly charts in 2005.

[42] 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.

[43] A chance meeting at a Lady Gaga concert before production began for the 2012 drama Monsters led Katori and Yamashita to co-author the drama theme song and formed a temporary unit named "The Monsters" to release the song as a single that would later top the Oricon weekly ranking.

[46] As of 2013, all three studio albums released by Yamashita received the RIAJ (Recording Industry Association of Japan)'s Gold certification, indicating a shipment of 100,000 copies.

Due to high demand from his fans, he added additional shows for Future Fantasy Yoyogi Arena in December, 2016[49] In April 2017, Yamashita and Kamenashi Kazuya reunited again after 12 years, naming their 2017 unit "Kame to Yamapi" and releasing "Senaka Goshi No Chance", the title song to their drama "Boku, Unmei no Hito desu ~ I'm your Destiny".