The Scream 4 actress and What's Your Number? producer Flynn will welcome the baby in spring 2012, reports People.
The couple told the publication that they "couldn't be more excited" to be expanding their family.
Shelton, who married Flynn in July 2001, gave birth to daughter West in September 2009.
She has starred in numerous film and TV projects throughout her career, including The Sandlot, Eleventh Hour, The Mighty Macs and A Perfect Getaway.
Shelton recently made a guest appearance in NBC's Harry's Law and will next be seen in Decoding Annie Parker alongside former Lost star Maggie Grace and The Muppets actress Rashida Jones.
Flynn also served as a producer on the long-awaited remake of 1980s war film Red Dawn, which was recently confirmed for a November 2012 release.
Watch a trailer for Scream 4 below: