Lyon was from 1975 until his death the chairman of Ruska Instrument Corporation. He was a major stockholder and later the chairman of the board of River Oaks Bank and Trust Company in the River Oaks section of Houston. He remained bank chairman until the institution was obtained in 1991 by Compass Bancshares.
A graduate of the former San Jacinto High School in Houston, later absorbed by the Houston Community College System, Lyon also attended Rice University and the University of Houston. He served in the United States Marine Corps. In 1962, the Junior Chamber of Commerce named Lyon among five "Outstanding Young Texans." In his real estate career, Lyon developed a number of Houston-area subdivisions, such as Spring Branch, Briarmeadow, Farnham Park, Tanglewilde, and Briarbend. In Galveston, he built the USS Flagship Hotel. He constructed the River Oaks Bank and Trust Company building and The Huntingdon, a 34-story Houston skyscraper completed in 1984.
In 1969, the Harris County GOP designated Lyon as its "Mr. Republican." Lyon was a delegate committed to Ronald W. Reagan at both the 1976 and the 1980 Republican National Conventions, which met in Kansas City, Missouri, and Detroit, Michigan, respectively. From 1968 to 1973, he headed the finance committee of the Harris County Republican Party.
Lyon was a member of the Petroleum Club, the Houston Club, the University Club, and the River Oaks Country Club. He founded the James E. Lyon Medical Research Foundation, which underwrites cancer research. He was also a board member of St. Joseph's Hospital Foundation, a member of the Rice University Associates, and a member of the president's council of Houston Baptist University.
Lyon died at his home in Houston at the age of sixty-five. He was survived by his wife, the former Desiree Dodson, a Georgia native, whom he married in a home ceremony on May 31, 1990. Prior to this marriage, Lyon for years had dated the singer Anita Bryant, a friend of Desiree's. Lyon's mother, Virginia Asbell Lyon Hedrick (1904-2000), survived him by some seven years. She was a native of Pierre, South Dakota, who was formerly a lecturer for the Dale Carnegie company. He also had three daughters from a previous marriage, Dana Lyon, Melissa Lyon Simon and her husband, Terry Simon, and Jennifer Stewart Lyon, all of Houston. Other survivors included a stepdaughter, Lelia Dodson; sister and brother-in-law, Connie Bruce and her husband, Homer Lindsay Bruce (since deceased); brother and sister-in-law, L. Willard and Chris Hedrick of Oceanside, California, and then six grandchildren.