Aside from group activities, Onew has participated in various television dramas, mostly known for his role of Baek Su in JTBCs sitcom Welcome to Royal Villa (2013) and the cardiothoracic resident Lee Chi-hoon in the popular KBS2 drama Descendants of the Sun (2016).
Onew was discovered at the 2006 S.M. Academy Casting. He received great appreciation from Lee Soo-man, S.M. Entertainment's founder, at Girls' Generation's debut showcase. Lee Soo-man noticed him and wanted to hear him sing during a one time on the spot audition. He signed the contract with the company the day after he auditioned. In 2008, he was chosen as the leader of the group Shinee, and the five member boy group debuted on May 25, 2008 on SBS's Inkigayo.
Shortly after debut, Onew contributed to singles for Lee Hyun-ji in 2008, for Vanilla LOVE and Vanilla Love Part 2. In 2009, he was featured with Girls' Generation member Jessica for the song One Year Later in the Tell Me Your Wish mini-album. The same year, he also sang a duet with Kim Yeon-woo for the song, The Name I Loved from the third mini album by Shinee, 2009, Year Of Us.
In 2010, Onew tried his hands at songwriting and together with his bandmate Minho, wrote the lyrics for the song, "Your Name" from Shinee's second studio album Lucifer. In addition to music, Onew became an MC of two programs – KBS2's Night Star, which he co-hosted alongside Shin Dong-yup, Yoon Jong-shin, movie director Jang Hang Joon, and Leessang's Gil and MBC's Show! Music Core. Since his first job as an MC, Onew has gained experience through the years and was active as a presenter for different television networks and events like Dream Concert, SBS's Incheon K-Pop Concert and also Mnet's special event in Taiwan called Nihao Taiwan.
Onew starred in various musicals starting from 2010, debuting in the musical Brothers were Brave alongside singer Lee Ji-hoon. He then starred in the Korean production of Rock of Ages playing the lead role, Drew. Onew has also showcased his acting skills via television like having a cameo role as a clumsy doctor in the drama Dr. Champ. He appeared in the drama's final episode. He also had cameo roles in the dramas Athena: Goddess of War, Oh My God x2, Pure Love and for sitcom Royal Villa. Also, Onew recorded a song titled In Your Eyes for the drama series To the Beautiful You. The song was released in the album To The Beautiful You OST Part 2 on August 22, 2012. Onew also sang the soundtrack Moonlight for drama Miss Korea. The song was released on January 3, 2014.
In January 14, 2014, his participation in the Borneo edition of the reality show Laws of the Jungle was confirmed. He was also in the cast for the Brazil edition, but had to leave and be substituted because of schedule conflicts. Additionally to his group activities and his job as a MC, Onew gained experience in radio hosting and took over shows like Kiss the Radio, a popular radio program aired on KBS Cool FM which is hosted by his labelmates Super Junior. In 2015, Onew was chosen out of more than 2,000 people as the main lead of a new web drama, Dating was the Easiest. The drama is adapted from a popular webtoon of the same title which revolves around the pure yet boisterous romance between a tiger spirit of the mountains and a high school girl. Onew was cast because of his unique analysis of the character and his determination whilst preparing for the auditions.
In 2016, Onew was cast in the drama, Descendants of the Sun, which starred Song Hye-kyo and Song Joong-ki. He portrayed first-year resident Dr. Lee Chi-hoon, a junior of Song Hye-kyo's character. The drama became a huge success especially in China where the series reached more than 2 billion views on the Chinese streaming site iQiyi. In Korea, the drama became a massive hit as well, surpassing more than 30 percent viewership ratings nationwide. Onew was awarded the "Newcomer Scene Stealer Award" at the 2016 Scene Stealer Festival for his role in Descendants of the Sun. Onew was also confirmed for a new tvN program Eat, Sleep, Eat which serves local recipes through Southeast Asia. On August 12, Onew and Lee Jin-ah released a duet, "Starry Night" as part of SM Station, a digital music project by S.M. Entertainment. It's a pop jazz song which is the work of numerous artists including Andreas Oberg, a Swedish guitarist and songwriter, and singer-composer Yoo Hee-yeol. In October 2016, Onew wrote the song "So Amazing" for his groups fifth Korean studio album 1 of 1 and another song, "Beautiful Life" for it's repackaged album, 1 and 1.
In May 2017 Onew and indie-duo Rocoberry released a song, "Lullaby" as part of SM Station.
In June, Onew was confirmed to join the cast of JTBC's Age of Youth 2. In the same month, Onew was featured in Heize's music video for the song "I Don't Know You". In August, 2017 shorty before the release of Age of Youth 2, Onew was accused of sexual harassment in a club and decided to leave the project after discussions with the production staff of the show. Due to his intoxicated state, Onew unintentionally came into physical contact with those around him, which caused a misunderstanding between him and another individual. The case has since been forwarded to the prosecution.
Onew underwent a vocal cord polyp removal and vocal fold mucosa reconstruction operation in June 2014, which made him unable to sing for a few months. In December, 2014, Kim Yeon-woo, Onew's vocal coach revealed during a radio broadcast that Onew's condition had improved after the surgery. He also said that Onew's vocal range "improved and he can make sounds comfortably too".
In order to support Onew in the musical Rock of Ages, in 2010, his fans had donated 1.44 tons of rice, a common practice for fans in South Korea, with the expectation that the idol will then donate to a charity of their choice — Onew donated it to help feed North Korean children, which was prepared by the Child Development Program. Onew also donated 770 kg of rice to children in need in South Korea in May 2010. In 2016, Onew donated roughly 1.2 million won to the Korean Heart Association.