The drama, based on a British series which ran from 2008 to 2010, has already received an order for one season from ABC.
Aytes and Macallan have now joined the cast and will play two of the four women at the center of the show, Deadline reports.
Aytes, who appeared in a previous attempted remake of Mistresses for Lifetime in 2009, will play a widow called April who juggles raising her daughters with running a shop.
Meanwhile, Macallan has landed the role of Josslyn, a real estate broker and "unapologetically sensual" woman.
Macallan has previously had guest roles in shows such as Shameless, Justified and Grey's Anatomy, while Aytes has starred in series like Drive, The Forgotten, Detroit 1-8-7, Desperate Housewives and ABC's short-lived comedy Work It.
Mistresses, which will air on ABC in 2013, is being penned by Gossip Girl writer KJ Steinberg.
> Only Fools and Horses, Misfits: The British invasion of US TV