Lowther first entered Parliament in 1865, as Member of Parliament for York. His maiden speech was against the Reform Bill of 1866, the failure of which brought down the ministry of Lord Russell. He also vehemently opposed the Reform Act 1867, brought forward by Disraeli and Lord Derby, but Disraeli nonetheless appointed him Parliamentary Secretary to the Poor Law Board the same year. He was a strong voice in the opposition to Gladstone, particularly to the Landlord and Tenant (Ireland) Act 1870. With the return to power of Disraeli in 1874, he was appointed Under-Secretary of State for the Colonies. In 1878, he was further advanced to become Chief Secretary for Ireland and sworn of the Privy Council of the United Kingdom and of Ireland. However, he was beset with difficulties during his tenure in the secretaryship. His opposition to the Land Bill was held against him, and he treated with contempt the agitation of the Land League, which would soon break out in the Land War. He went out of office with Disraeli's government in 1880, and lost his seat at York as well.