The 69-year-old, who is one of the longest-serving stars of the BBC One soap, said leaving the show would be like "a bereavement".
Pat, known for her dangly earrings and bright make-up, first appeared in 1986.
During her colourful years on the show, the character remarried several times and went to prison.
"I have enjoyed 25-and-a-half wonderful years in EastEnders creating the character of Pat, but feel it's time to hang up her earrings," St Clement said.
"Leaving the EastEnders family will be akin to a bereavement. But I'm looking forward to the other work and life opportunities that I will have the time to pursue."
Pat's most famous storylines in the show have included her rocky relationships with Frank Butcher (Mike Reid), and with her step-daughter Janine (Charlie Brooks).
She also endured a sometimes strained friendship with Peggy Mitchell, who was played by Barbara Windsor.
It has not been disclosed how the character will exit the soap, although Bryan Kirkwood, executive producer of the programme, said the departure would be "fitting".
John Yorke, controller of BBC drama production, said: "It's always a sad day when one of our stars leaves EastEnders, but when those stars are as important as Pam St Clement and the character as iconic as Pat Butcher, the blow is doubly hard."
He added that Pat had been "integral" to the programme's success and her earrings had become "part of British culture".
"For most actors that would be legacy enough. The fact that Pam is also a total professional, an endless champion of the programme and a joy to work with is an added bonus."
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