Song Chang-eui debuted as a musical theater actor in Blue Saigon in 2002. He gained fame for his portrayal of a transgender rocker in the 2006 production of Hedwig and the Angry Inch. In 2007, he starred in the SBS series Golden Bride, which won him Best New Actor for TV at the 44th Baeksang Arts Awards. In 2009, he and Lee Wan headlined the movie Once Upon a Time in Seoul, which earned him the Best New Actor trophy at the 17th Chunsa Film Art Awards. In 2010, he played an openly gay doctor in the SBS series Life Is Beautiful, in which he was recognized with an Excellence Award at the SBS Drama Awards. In 2014, he bagged another Excellence Award at the SBS Drama Awards for his work in Thrice Married Woman. In 2015, he took home a Top Excellence Award at the MBC Drama Awards for his performance in Make a Woman Cry. In 2017, he led the KBS2 series The Secret of My Love, in which he received an Excellence Award at the KBS Drama Awards.

Song Chang-eui married his non-celebrity girlfriend on September 5, 2016. They have a daughter together.