DeGuglielmo was part of two Super Bowl-winning teams in his coaching career; the 2007 New York Giants and 2014 New England Patriots.

One of three children (an older brother Charlie, and younger a Sister Cristina), he is first generation Italian-American, as his father (Carmine Giuseppe DeGuglielmo / legally changed his name to Charles Joseph DeGuglielmo) emigrated to the US in 1954 with his family as a teenager, from a village outside of Avellino, Italy.

His mother (June Dorothy Galassi) was born in Boston, and of Italian and French Canadian heritage.

[7] On January 22, 2014, the New England Patriots announced they had hired DeGuglielmo as the new offensive line coach to replace Dante Scarnecchia, who retired after 30 years with the team; DeGuglielmo had a preliminary agreement to serve as offensive line coach at University of Maryland six days prior to the Patriots' announcement.

[11] On July 29, 2019, just four days into training camp, the Miami Dolphins dismissed offensive line coach Pat Flaherty and promoted DeGuglielmo to the position.

[12] DeGuglielmo was hired as the Giants offensive line coach under Joe Judge midway through the season, replacing the terminated Marc Colombo.

[15] In February 2022, DeGuglielmo was hired as the offensive line coach on Jeff Hafley's staff at Boston College.

[17] On February 17, 2024, it was revealed that DeGuglielmo would serve as the offensive line coach for the Birmingham Stallions of the United Football League (UFL).