Han Ga-in made her entertainment industry debut in an Asiana Airlines commercial in 2002 before landing her first acting role in the KBS2 drama Sunshine Hunting. In 2003, she bagged a supporting role in the popular KBS1 daily series Yellow Handkerchief, which won her Best New Actress at the KBS Drama Awards. In 2004, she made her big screen debut in the drama film Once Upon a Time in High School, which earned her Best New Actress nominations at the 25th Blue Dragon Film Awards and the 3rd Korean Film Awards. That same year, she acted alongside Chae Shi-ra in the KBS2 drama Terms of Endearment, in which she won an Excellence Award at the KBS Drama Awards. In 2005, she took home another Excellence Award at the MBC Drama Awards for her work in Super Rookie. In 2012, she was paired with Kim Soo-hyun in the hit MBC sageuk The Moon That Embraces the Sun, which was named Best Drama at the 48th Baeksang Arts Awards. Her performance in the series gave her a Top Excellence Award at the MBC Drama Awards. Also in 2012, she starred in the blockbuster film Introduction to Architecture.

On April 26, 2005, 23-year-old Han Ga-in married her Yellow Handkerchief co-star Yeon Jung-hoon. She suffered a miscarriage in May 2014. In April 2016, she gave birth to a baby girl. In May 2019, she and her husband welcomed their son.