Eunhyuk was born Lee Hyuk-jae in Seoul, South Korea. He has an older sister Lee So-ra. Raised in a family that struggled financially, he was interested in street performing as a child. Inspired by the likes of H.O.T's Jang Woo-hyuk, Michael Jackson and singer-dancer Yoo Seung-jun, Eunhyuk trained himself at a young age.

On 26 February 2010, Eunhyuk was diagnosed with H1N1 influenza, but was set to appear as a guest at label mate Girls' Generation's Into the New World encore concert in Seoul, hence had to pull out and was replaced by bandmates Leeteuk and Heechul. Super Junior released their 4th studio album, Bonamana, with similar success in Korea, sweeping awards in music programs after the release date. Their follow-up song, Boom Boom, was choreographed by Eunhyuk and performed on music programs Inkigayo and Music Core. On October 8, 2010, the digital single 'Angel' for HARU OST was released, with Eunhyuk featuring a rap verse.  In 2011, Eunhyuk, along with Sungmin was placed two new members of Super Junior-M. On 27 September 2011, he along with Yesung and Shindong filled in for bandmate Heechul, who enlisted for mandatory military service on 1 September, during the performance on Music Bank and Show! Music Core of Kim Jang-hoon latest single, "Breakups are So Like Me". Heechul is featured in the song and starred in the music video, which was completed the day before he enlisted. Mr. Simple, Super Junior's award-winning 5th studio album, was promoted heavily with Eunhyuk participating in much of the album's production through choreography, and rap lyrics for the track, Oops. The album sold over 500,000 units and won the Disk Daesang Award at the 26th Golden Disk Awards and 21st Seoul Music Awards, as well as Album of the year at the 13th Mnet Asian Music Awards. The album is listed as the 2nd best-selling album as of the year 2011.  In November, Eunhyuk made his musical theatre debut in Fame, where he played Tyrone Jackson, along with Tiffany of Girls' Generation, Son Ho Young, Lina of The Grace and Kim Jung Mo of TRAX. It was on at the Woori Financial Art Hall from 25 November 2011 to 29 January 2012. It was announced on 30 November 2011 that after five years, he and Leeteuk would leave Super Junior's Kiss the Radio and was replaced by fellow members, Sungmin and Ryeowook on 4 December 2011.

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