[2] Virginia attended Drexel University, majoring in business management[3] with the aspiration of serving as her father's secretary.

[4] She was an active member of the local Pi Sigma Gamma sorority, the Newman Club, the Panhellenic Council, and the YWCA.

[14] In 1986, she disbanded the team's cheerleading squad, the "Honey Bears", after ten years, arguing that their field performances were "sexist and degrading to women".

[16] Her son Michael McCaskey was team president from 1983 to 1999, when Virginia fired him,[17][15] though he remained as chairman of the board until May 6, 2011, when his brother George assumed the position.

She called it "her happiest day so far", after the Bears had beaten the New Orleans Saints to earn a trip to Super Bowl XLI.

[23] McCaskey was one of ten female NFL owners in 2022, including Sheila Ford Hamp (Detroit Lions), Amy Adams Strunk (Tennessee Titans), Kim Pegula (Buffalo Bills), Carol Davis (Las Vegas Raiders), Denise DeBartolo York (San Francisco 49ers), Gayle Benson (New Orleans Saints), Janice McNair (Houston Texans), Jody Allen (Seattle Seahawks), and Dee Haslam (Cleveland Browns).

[27] McCaskey was known for being "proudly private" pertaining to the team her father built, rarely discussing the business aspect of her life.