Graduating from Bloomfield High School in 1950, Rome earned his Bachelor of Arts degree in history from the University of Connecticut in 1954 and his Bachelor of Laws (LLB) degree from the University of Connecticut School of Law in 1957.

Four years later, Rome ran a spirited campaign for governor but lost the 1982 election to O'Neill, despite receiving endorsements from fifty-nine of Connecticut's leading newspapers as well as from the New York Times.

Serving until 1997, Rome was instrumental in securing passage of the UConn 2000 legislation, which committed $1 billion in state funding to renew the university's infrastructure.

[9] The Lewis B. Rome Commons building and ballroom on UConn's Storrs campus was named in his honor.

[11] He died following a long illness on July 1, 2015, and was interred at the Beth David Cemetery in Wethersfield, Connecticut.

In 1954 he married Ann Kathleen (Nicolle) Rome, with whom he had four children; David, Deborah, Richard, and Thomas.