"Jennifer Connelly is one of the great actresses of our time. We always wanted her to play Dawn in American Pastoral and we're thrilled to be working with her," Lakeshore Chief Executive Officer Tom Rosenberg said in a statement Monday.
Phillip Noyce is directing the film, which is based on Philip Roth's Pulitzer Prize-winning novel.
Connelly will play Dawn, a former beauty queen and the wife of McGregor's Swede Levov, a legendary high school athlete who inherits his father's business as an adult.
"Swede's seemingly perfect life shatters when his daughter rebels by becoming a revolutionary and commits a deadly act of political terrorism during the Vietnam War," a synopsis said.
With a screenplay by John Romano, filming is scheduled to begin in Pittsburgh next March.
Connelly's most recent films include Winter's Tale and Noah. She is best known for her Oscar-winning performance in A Beautiful Mind.