After the Irish Rebellion of 1641, Galway was in a delicate position, caught, in effect between the Catholic rebels (Confederates) and its English garrison ensconced in Fort Hill just outside the city. Eventually, Galway citizens, who were predominantly Catholic, went against their garrison and supported the confederate side in 1642. The fort was besieged with the aid of Confederate troops until it surrendered and its garrison was evacuated by sea. During the 1640s, Galway was heavily fortified against an expected counter-attack by English forces, which eventually materialised when English Parliamentarian forces re-conquered Ireland in 1649-52. Galway surrendered to Cromwellian forces in 1652 after a nine-month siege; plague and expulsions of Catholic citizens followed. The Cromwellian Act of Settlement 1652 caused major upheavals, as peoples from east of the Shannon were transplanted to Connacht and slipped back.
After the demise of the English Commonwealth and the English Restoration in 1660, (and the further Act of Settlement 1662 and its Act of Explanation 1665), the economy of Galway recovered somewhat. In the next crisis, centred around the deposition of the Catholic King James II, in 1689, Galway supported the Jacobite side. It surrendered without a siege under the Articles of Galway of 1691 after the annihilation of the main Jacobite army at the nearby battle of Aughrim. Thereafter, the city become an economic backwater, and the capital of its old great families were spent overseas. It took about 300 years for the city to regain its former status.

