Pombal secured his preeminence through his decisive management of the 1755 Lisbon earthquake, one of the deadliest earthquakes in history; he maintained public order, organized relief efforts, and supervised the capital's reconstruction in the Pombaline architectural style. Pombal was appointed as Secretary of State for Internal Affairs in 1757 and consolidated his authority during the Távora affair of 1759, which resulted in the execution of leading members of the aristocratic party and allowed Pombal to suppress the Society of Jesus. In 1759, Joseph granted Pombal the title of Count of Oeiras and, in 1769, that of Marquis of Pombal.

A leading estrangeirado strongly influenced by his observations of British commercial and domestic policy, Pombal implemented sweeping commercial reforms, establishing a system of companies and guilds governing each industry. These efforts included the demarcation of the Douro wine region, created to regulate the production and trade of port wine. In foreign policy, although Pombal desired to decrease Portuguese reliance on Great Britain, he maintained the Anglo-Portuguese Alliance, which successfully defended Portugal from Spanish invasion during the Seven Years' War. He expelled the Jesuits in 1759, created the basis for secular public primary and secondary schools, introduced vocational training, created hundreds of new teaching posts, added departments of mathematics and natural sciences to the University of Coimbra, and introduced new taxes to pay for these reforms. Pombal enacted liberal domestic policies, including the prohibition of the import of black slaves within Portugal and Portuguese India, and greatly weakened the Portuguese Inquisition, and granting civil rights to the New Christians. Despite these reforms, Pombal governed autocratically, curtailing individual liberties, suppressing political opposition, and fostered the slave trade to Brazil. Following the accession of Queen Maria I in 1777, Pombal was stripped of his offices and ultimately exiled to his estates, where he died in 1782.