Oh Ji-ho started out as a commercial model before making his acting debut with a small role in the 1998 film Naked Being. In 2004, he won Best Supporting Actor at the KBS Drama Awards for his work in Second Proposal. In 2006, he starred in the MBC romantic comedy Fantasy Couple, opposite Han Ye-seul. His performance in the series earned him an Excellence Award nomination at the MBC Drama Awards. In 2010, he became part of the award-winning KBS2 sageuk drama Chuno, in which he bagged an Excellence Award at the KBS Drama Awards. In 2013, he led the KBS2 series God of the Workplace, which scored him acting trophies at the KBS Drama Awards and the 21st Korea Culture and Entertainment Awards. In 2019, he appeared in the MBC drama No Second Chances, in which he was nominated for a Top Excellence Award at the MBC Drama Awards and the 7th APAN Star Awards.

In January 2007, Oh Ji-ho’s ex-girlfriend committed suicide after their breakup. In April 2014, the actor married his fiancée who works in the fashion industry. They have a daughter and a son together.