The tearful Benidorm actress said on air it was "kind of time" to leave and she had "said everything there is".
"I have a thing that goes right through my body that says Loose Women, like a [stick of] rock in Blackpool, and so it will never, ever leave me," she added.
The 65-year-old, who has appeared on the lunchtime show since 2003, will bow out on 5 September.
Yet she hinted she might return in future by saying: "Like Arnold Schwarzenegger said, 'I'll be back'."
Hewson thanked her fellow panellists on Wednesday's programme as she made her emotional announcement.
"We all care about each other," said the former Coronation Street star. "We all look after each other.
"We've all been there for each other and stood by their side and made sure that they're okay."
Hewson will be seen later this year in a one-off Are You Being Served? special, playing the Mrs Slocombe role Mollie Sugden played in the original BBC sitcom.
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Loose Women panellist Sherrie Hewson has announced she is to leave ITV's talk show later this year.