Lee Min-ki began his acting career by appearing in drama specials. In 2005, he became part of the MBC daily series Be Strong, Geum-soon, in which he won Best New Actor at the MBC Drama Awards. In 2007, he earned Best New Actor nominations at the 43rd Baeksang Arts Awards for his work in the series Love Truly and the 28th Blue Dragon Film Awards for the movie A Good Day to Have an Affair. That same year, he landed a main role in the KBS2 romantic comedy Dal Ja’s Spring, in which he was nominated for an Excellence Award at the KBS Drama Awards. In 2009, he starred in the hit disaster film Haeundae, which scored him a Best New Actor trophy at the 46th Baeksang Arts Awards. In 2017, he played his first small screen leading role in 10 years in the tvN series Because This Life Is Our First, opposite Jung So-min.

Aside from acting, Lee Min-ki also ventured into singing. In 2009, he released his first extended play No Kidding, which featured six tracks. He also lent his voice to the official soundtracks of some of his acting projects.

In 2014, Lee Min-ki revealed in the JTBC talk show Witch Hunt that he was once in a relationship with a woman six years older than him. He enlisted for his mandatory military service in August 2014 and was discharged in August 2016.