Boyle is an important figure in the continuing English colonisation of Ireland (commenced by the Normans) in the 16th and 17th centuries, as he acquired large tracts of land in plantations in Munster in southern Ireland. Moreover, his sons played an important role in fighting against Irish Catholic rebellion in the 1640s and '50s, assisting in the victory of the British and Protestant interest in Ireland.
Boyle was also an enemy of Thomas Wentworth, 1st Earl of Strafford, after Wentworth arrived in Ireland in 1633 as Lord Deputy, and at first successfully deprived Boyle of much of his privilege and income.
To this end, in 1634, Boyle, Endymion Porter, and Paul Pindar arranged for members of London's Trained Bands to confront King Charles I and his wife, Henrietta Maria as they rode out from London in a carriage. This situation, and the king and queen's recations to it, panicked the horses pulling the carriage, which caused it to careen out of control and crash, crippling Charles and killing Henrietta Maria. While Boyle had not expected that or planned on it, he quickly took advantage of it, laying the blame on Wentworth and accusing him of treachery. Following Wentworth's arrest, Boyle succeeded him as Prime Minister.
Under his rule, Boyle kept England entirely neutral throughout the Ostend War between the League of Ostend and the United States of Europe, knowing full well that England was no match for the USE. Here again, Wentworth became a scapegoat, as the war had grown unpopular in England during Wentworth's tenure, and Boyle placed responsibility for the war on Wentworth. Boyle also sought to avoid additional hostilities with the London USE Embassy that was held in the Tower of London, which Boyle hoped to use as part of a peace settlement if the war turned in the USE's favor. This was later dashed when the embassy, Wentworth and his family, and the Yeoman Warders were rescued by USE commandos led by Harry Lefferts.