Molyneux joined the Royalist army at the outbreak of the English Civil War, and served with his brother in the Lancashire Regiment, which was mostly Catholic, through almost all the fighting from Manchester (1642) to Worcester (1651).
As a well-known Catholic Cavalier, he experienced harsh treatment from the victors; and the family estates suffered.
He was then appointed Custos Rotulorum of Lancashire (1685–89), Lord Lieutenant of Lancashire (1687–1688) and Admiral of the Narrow Seas, and was one of the few who fought with any success on James's side against the Prince of Orange, seizing and holding Chester, until all further resistance was in vain.
After using the castle to store arms, he was arrested on a fabricated charge of treason for a suspected Jacobite rebellion called "The Lancashire plot".
He did not however recover the hereditary constableship, and the castle was leased to the burgesses, who in 1704 were authorised by the Crown to destroy it.