Hughes began working for Bush in 1994
Mrs Hughes, 45, who served as counsellor to the president and is widely thought to be one of his most trusted aides, said that it had been a tough decision but she had wanted to spend more time with her family.
"My husband and I have made a difficult but, we think, right decision to move our family home to Texas," she said.
"I'll be honest: I guess we're a little homesick."
'Never settled'
Mrs Hughes is reported to have told friends privately she was concerned that her family, especially her son, had never settled in Washington and that she missed her stepdaughter and granddaughter, Reuters news agency reported.
In Washington, general consensus seemed to be that Ms Hughes wished to depart the city's political scene for genuine reasons, not due to any political disagreement.
Ms Hughes stressed that she intends to continue advising the president on communications strategy both from her home in Texas and in visits to Washington.
And, in a later interview, Mr Bush said that despite Ms Hughes' departure she was still considered a valid part of his government.
"She may be changing addresses, but she's not leaving my inner circle," he told The Associated Press news agency, adding that Mrs Hughes had handed in her resignation late last week and he had accepted.
A former television reporter, Ms Hughes began working for Mr Bush in 1994, rapidly becoming one of the president's closest advisors.
She is thought to have co-written many of his most important speeches that set out his political agenda, including one he addressed to the American people two weeks after the 11 September attacks in New York and Washington.
No-one has been immediately named as her successor to the position of counsellor to the president.