Elizabeth sent an army of 20,000 to quell the rebellion, first under the Earl of Essex and then under Lord Mountjoy, a ruthless strategist. In 1600 O'Neill marched north from Munster to assist O'Donnell who was fighting against an English garrison in Derry. In September the same year the help long promised by Philip of Spain landed at Kinsale, Co. Cork, but the Spaniards were soon under siege from Mountjoy and his forces.

O'Neill and O'Donnell marched the length of Ireland in the depth of winter to attack the English in an attempt to lift the siege. A brief and bloody battle on Christmas Eve 1600 ended in defeat for the Irish. Red Hugh O'Donnell fled Ireland with the Spanish survivors and O'Neill returned to Ulster, his army in tatters