The 47-year-old joined the show in 1993 as a US entertainment correspondent and landed the job of the show's main presenter three years later, replacing Anthea Turner.
Phillips said in a statement: "I love the job but I've got other responsibilities - the children, a home life and an elderly dad who needs me - and I've recognised that I can't have it all."
She added that leaving the breakfast show was "the hardest decision I have ever made".
Peter McHugh, GMTV's director of programming, said: "After all those years of getting up at 4am we can understand why she wants a change. Her honesty and openness have helped make GMTV the success it is. She is a tough act to follow."
Phillips will leave GMTV at the end of the year.