In Co. Wexford, due to the conflicting messages emanating from Dublin, there was considerable confusion as to whether the Rising was to take place or not. Eventually, early on Easter Monday Mrs Jennie Wyse-Power, a member of Cumann na mBan, relayed a message from Pearse that the Rising would indeed take place that day; that night news arrived that the Rising was in progress.

On Wednesday a message arrived from James Connolly requesting that the Enniscorthy Volunteers hold the railway line from Rosslare to prevent British reinforcements reaching Dublin. On Thursday the Enniscorthy Volunteers together with contingents from other areas took over Enniscorthy, establishing headquarters in the Athenaeum, a strong position beside the castle. The Volunteers were supplemented by members of Fianna Éireann and Cumann na mBan. Brigade Commandant Robert Brennan was the officer in charge. The Volunteers took over the town and blocked the roads and the railway line. They surrounded the Royal Irish Constabulary barracks and exchanged fire with the police; they did not, however, attempt to capture the barracks, believing that in time the RIC would surrender. Meanwhile, a force under Captain Paul Galligan occupied the town of Ferns and some of the northern part of the county.

On Saturday news of the general surrender in Dublin reached Enniscorthy. The Volunteers required that the surrender be confirmed: the following day the British escorted Captain Seamus Doyle and Captain Seán R. Etchingham to Dublin to consult Pearse in Arbor Hill. On Monday, 1 May, the Enniscorthy Volunteers surrendered unconditionally. While a number of the officers were sentenced to death, all had their sentences commuted.