Yoo Ji-tae started out as a model before debuting as an actor in the 1998 movie Bye June. He quickly rose to fame with his remarkable acting in the 1999 crime-comedy film Attack the Gas Station, in which he was nominated for Best New Actor at the 20th Blue Dragon Film Awards. This was followed by a leading role in the 2000 sci-fi romance movie Ditto, which won him Best New Actor at the 8th Chunsa Film Art Awards and the 1st Busan Film Critics Awards. In 2014, he appeared in the KBS2 series Healer, in which he was nominated for an Excellence Award at the KBS Drama Awards. In 2017, he was named Best Actor at the 11th Cable TV Broadcasting Awards for the tvN drama The Good Wife. That same year, he led the KBS2 action series Mad Dog, which earned him a Top Excellence Award nomination at the KBS Drama Awards.

Aside from acting, Yoo Ji-tae also directs and writes screenplays for films. His first directorial job was the 2003 short film The Bike Boy, which received the Audience Award at the 20th Busan Asian Short Film Festival. In 2013, he made his feature film directorial debut in the movie Mai Ratima. The film, which was based on a synopsis Yoo Ji-tae wrote in college, won the Jury Prize at the 2013 Deauville Asian Film Festival.

Yoo Ji-tae was singlehandedly raised by his mother. He married actress and model Kim Hyo-jin on December 2, 2011. They welcomed their first son in 2014 while their second son was born in 2019.