The two-part drama - written by Chris Lang (Hustle) - will focus on the aftermath of a shocking murder.
When Rosie (Norris) discovers a pair of bloodied trainers in her home, she begins to suspect that her son Jamie - played by Skins actor Alexander Arnold - may be responsible for the death of a teenage schoolgirl.
Doc Martin star Clunes will play Rosie's new husband Ben, while Paul McGann (Doctor Who) will also star as her ex-husband and unlikely confidante David.
"A Mother's Son is the story of an ordinary mother tormented by her suspicions and thoughts that her son may be capable of murder," said ITV Drama's Victoria Fea.
"She's confronted with this terrifying dilemma and has to ask herself, should she go to the police and give him up? She'll wrestle with this throughout what is a very compelling drama."
"Chris Lang has written a beautifully, compelling script," added ITV Studios exec producer Myar Craig-Brown. "We're delighted Martin Clunes and Hermione Norris have agreed to play Ben and Rosie."
A Mother's Son is filming on location in London and Suffolk.