Callard, 53, began playing Liz McDonald in 1989. She left the show in 1998, but returned in 2003.
The BBC quoted the actress as saying she will leave the role permanently next year because she wants to see "what life has to offer beyond Liz's famous mini skirts."
"I've loved every minute of my second stint on the 'Street.' It's always a difficult decision to make the leap. I'll miss everyone on the show, but I'm looking forward to some new challenges," she said.