Mayes Middleton resides in Galveston with his wife, Macy, and four children, Connor, Christian, Matthew, and Martha Ann. Mayes is president of Middleton Oil Company, an independent oil and gas company. He also runs ranching, cattle, and farming operations. Mayes and his wife support numerous local community organizations and faith-based charities.
Before his election to the Texas Senate in 2022, Mayes was first elected to the Texas House of Representatives in 2018 to represent House District 23, encompassing Chambers County and part of Galveston County. In his two terms in the Legislature, Mayes has consistently ranked as one of the top 10 most conservative members of the Texas House. During his most recent term in the House, Mayes served as the Chairman of the Texas House Freedom Caucus.