Chow, a former Toronto city councillor who represents the Trinity-Spadina riding for the NDP, will formally launch her campaign on Thursday in the Toronto neighbourhood in which she grew up, St. Jamestown.
Chow had previously said she was "seriously considering" a run for mayor but was waiting to make a decision.
Chow's campaign will be headed by veteran Conservative strategist John Laschinger, while her war room will be run by Warren Kinsella, a well-known Liberal.
Chow is considered a front-runner in the already crowded field that includes Ford, one-time provincial Conservative leader and failed mayoral candidate John Tory, city councillor Karen Stintz and former councillor David Soknacki.
Chow's late husband, former NDP Leader Jack Layton, was elected to Toronto city council in 1982 and had a failed mayoral bid in 1991. Chow's stepson Mike Layton is a sitting councillor.
Chow, the NDP's current Transport critic, has a long history as a Toronto councillor herself. She was the first Asian woman elected to Metropolitan Toronto Council, in 1991, and she was re-elected five times before winning a federal seat in 2006.
She was chair of the community services committee and vice-chair of the Toronto Transit Commission.
Chow's website boasts that "she was central in forging nine consecutive balanced budgets as a member of the city’s budget committee from 1994 to 2003."