González was born in Matamoros, Tamaulipas, Mexico. He began his military career in 1847, fighting the invaders from the United States in the Mexican-American War after they killed his father, a farmer. From 1853 to 1855, he fought with the Conservative forces supporting General Antonio López de Santa Anna. At the time of the Plan de Ayutla in 1854, he was with Conservative General Leonardo Márquez in Oaxaca, fighting against Liberal general Porfirio Díaz.

In 1856, he was wounded at the Battle of Ocotlán (1856), fighting with rebels against President Ignacio Comonfort. In March 1859, he took part in an attack on Veracruz by Conservative General Miguel Miramón, against the legal, Liberal government of President Benito Juárez. In 1860, he took advantage of an amnesty for the Conservatives decreed by Congress and offered his services to the Liberals fighting against Maximilian of Habsburg and the invasion.

During his term, the Constitution of 1857 was amended to remove the right of succession to the presidency from the office of President of the Supreme Court, which was how both Benito Juárez and Sebastián Lerdo de Tejada had come to the presidency. Instead, the President of the Senate was named next in succession, or the President of the Permanent Commission, in the event that the Senate was in recess.

González served under the military command of Porfirio Díaz. He participated in the defense of Battle of Puebla Puebla on May 5, 1862 against the French, where the Mexicans won a great and unexpected victory. He was wounded and taken prisoner, but escaped. In 1863, Díaz made him chief of the Army of the Center. He fought under Díaz in the battles of Miahuatlán and La Carbonera, Oaxaca.

González was taken prisoner by the French a second time in 1865, but he was paroled and rejoined the Mexican army. In 1867, he participated in the sieges of Puebla (where he lost his right arm) and of Mexico City. On 7 September 1867, after Juárez's forces had retaken the capital, Juárez named him military commander of the Federal District and governor of the National Palace, serving from 1871-1873. He supported Díaz in revolt under the Plan de la Noria (Díaz's 1871 unsuccessful revolt against Juárez) and the Plan of Tuxtepec (his successful 1876 revolt against then-President Sebastián Lerdo de Tejada). Vicente Riva Palacio, liberal Politician, intellectual, and military man, served in his government.

On 13 March 1877, he obtained the rank of general of division. Díaz named him governor and military commander of Michoacán (1877–79) and secretary of war and the navy (28 April 1878 to 15 November 1879).

Porfirio Díaz could not run for re-election in 1880, and chose his comrade-in-arms González as the presidential candidate, who was duly elected. He served from 1 December 1880 to 30 November 1884, both proceeded and succeeded by Porfirio Díaz. Díaz was a minister in his government.

Under González, Mexico re-established relations with European powers (Britain, France, Germany), which was an important means to offset U.S. power in Mexico as well as gain access to European capital. Mexican relations with Great Britain were renewed, once Mexico recognized the long-standing British bond debt from the Conservative government. The considerable sum of £11.5 million would be a drain on the empty national treasury, with the announcement coming during a financial downturn in Mexico. This concession provoked protests from the Mexican congress, and riots in the capital put down forcefully and brutally, damaging González's reputation. Aiding in the economic expansion of Mexico was the founding of the Banco Nacional de México, with French Bankers playing an important role. The preference for ties with Europe was reinforced with Mexico's adoption on 20 December 1882, of the metric system of measurements, created under French Emperor Napoleon, rather than the British/U.S. measurements.

In 1882, he issued nickel coins, replacing silver coinage, which produced the inflation rate and prompted the devaluation of the currency, provoking riots on 21 December 1883. With his characteristic valor, he appeared before the rioters, actually receiving cheers before he finished speaking.

After his term as President, he was charged of misappropriation of public funds by the Congress and the case was referred to a Grand Jury, but the charges were never pressed. Rather than being punished by the legal system, González was elected governor of Guanajuato "unanimously" in 1884 and served three terms in office until his death in 1893, He made a failed attempt to succeed President Díaz in 1887.

At the end of his full four-year term, he stepped down from presidency and was succeeded by Porfirio Díaz, who had not been re-elected to consecutive terms as President, but following the González interregnum, Díaz would remain in power until ousted in 1911 with the outbreak of the Mexican Revolution in 1910. Díaz's denigration of González's achievements as President and the charges of corruption have led to his basic eclipse in Mexican history. His biographer Don M. Coerver's full scholarly study of his presidency is an exception.