Apart from Jimmy Kimmel Live!, he has also produced shows such as Crank Yankers, Sports Show with Norm Macdonald, and The Andy Milonakis Show.
James married Gina Maddy in 1988. However, their relationship did not last long and they divorced in 2002, nearly after four years of marriage.
He has a daughter Katherine (born in 1991) and a son Kevin (born in 1993) with Gina. From 2002 to March 2009, James dated comedian Sarah Silverman.
In October 2009, James started dating Molly McNearney, a co-head writer for Jimmy Kimmel Live. The couple got married in the month of July 2013.
With Molly McNearney, James shares two kids. Their first daughter Jane was born in the month of July 2014 and a son William John, was born on April 21, 2017.
Their son was born with a rare congenital heart defect, tetralogy of Fallot (TOF) with pulmonary atresia. The defect was detected three hours after birth.
After three days after the birth, he underwent successful surgery. Cardiac surgeon Mehmet Oz was the first guest James welcomed on his show after his son's birth.