The Cameron machine, later known as the Quay machine and Penrose machine, was a Republican political machine in Pennsylvania that controlled much of the state's politics for seven decades. Founded by antislavery Know Nothing and Republican Simon Cameron, it passed into control of his son J. Donald Cameron, later controlled by Matthew Quay and finally Boies Penrose. The organization was financially and fiscally conservative, favoring higher protective tariffs and representing business interests.

The elder Cameron's leadership skills were contrasted with the weaker political abilities of his son Donald, and several Republican defeats resulted in a transfer of machine power into the hands of Quay, who utilized the machine's powers with shrewd effectiveness. The baton of machine boss was then passed for a final time to Penrose, whose death ended its power and influence.

The state Republican machine of Pennsylvania was first established by Simon Cameron, originally a Jacksonian Democrat who became a Know Nothing and eventually joined the Republican Party. Cameron, who previously in 1845 organized a coalition of Whigs, anti-Catholic activists, and protectionist Democrats that elected him to the Senate, rode the coattails of the rising Republican Party influence around 1860 to form the machine that would prove influential for decades to come.

Previously a businessman, Cameron wielded power over state jobs and contracts to exert and cement his influence after his election to the United States Senate in the 1866 elections. Among patronage decisions, he transacted loans from Middletown Bank to loyal Republicans.

In 1877, J. Donald Cameron became a U.S. senator from Pennsylvania following the resignation of his father. Despite obtaining such an important post in addition to assuming leadership of the elder Cameron's political machine (which resulted in effectively being the Pennsylvania Republican Party "boss"), his political skills were lacking, in addition to charisma. While a consistent party loyalist, Cameron seldom spoke on the Senate floor or introduced legislation.

Although generally quiet, Cameron was outspoken in his support for protective tariffs, a position held by most Republicans.

During the 1880 presidential election, Cameron served as the chairman of the Republican National Committee. Aligned with congressional conservative stalwarts led by Roscoe Conkling, he supported nominating former president Grant to run for an unprecedented, non-consecutive third term.

In 1882, factionalism divided the Pennsylvania GOP and handed a victory to Democrats when roughly 40,000 Liberal Republicans, pejoratively deemed "Half-Breeds" by the Republican machine, bolted from the party in the gubernatorial election that year to vote for an "Independent Republican" candidate. Several years later in the mid-1880s, Cameron was replaced as machine leader by Matthew S. Quay, who proved to surpass the former in influence and capabilities.