She will appear in ITV's The Widower about Malcolm Webster, who was jailed for life in 2011 and recently lost an appeal against his conviction.
Reece Shearsmith will play Webster who killed his first wife Claire Morris (Smith) and attempted to kill his second wife, in the three-part series.
In 2012, Smith - who co-starred with David Morrissey in this week's BBC romantic drama The 7.39 - was seen as the wife of another real-life criminal when she played the title role in Mrs Biggs, partner of Great Train Robber Ronnie who died last month.
Male nurse Webster married his first wife in 1993 but went on to drug her over a period of time, leaving her unable to challenge him about how he was living beyond his means. He then plotted a car crash which killed her the following year, but was thought at the time to have been an accident.
He later settled in New Zealand, attempting to embark on a similar scheme to cash in on insurance payments, as he had done on the previous occasion. His second wife Felicity Drumm survived the attempt in 1999 but he fled, eventually surfacing in Scotland and trying to woo another woman, Simone Banarjee.
Also appearing in the series are John Hannah, who plays a detective on Webster's trail, and Archie Panjabi, who portrays Ms Banarjee.
Ms Banarjee was a consultant on the series, along with Ms Drumm, who is played on-screen by Kate Fleetwood.
Jeff Pope, executive producer and head of factual drama for ITV Studios, said: "This is a quite extraordinary story, far more chilling than any fiction. Webster was a banal, almost benign, face of evil.
"He was so clever at hiding his tracks and presenting a plausible front to his friends, family and colleagues that he was able to do what he did without really attracting suspicion.
"The courage and tenacity of Webster's second wife Felicity, and his last intended victim Simone, is all that stood between him and potentially more murders."
It will be filmed in Scotland, Auckland in New Zealand, and Guildford in Surrey.