A member of the conservative wing of the Radical Party since his high school days, he was elected local president of the youth branch of that party and later city councillor. During the presidential election of 1920 he campaigned for Arturo Alessandri, being responsible for the southern part of the country. He was rewarded by Alessandri with the appointment of Consul-general and Chargé d'affaires to Panama. On October 21, 1921 he married Marta Ide, and together they had three sons: Juan, Carlos and Fernando.
He returned to Chile in 1924, in order to run in that year's congressional elections. Ríos resulted elected as deputy for Arauco, Lebu and Cañete being reelected in 1926. After Alessandri's return to power following the Chilean coup of 1925, he participated of the committee charged with drafting a new constitution, that led to the approval and proclamation of the 1925 Chilean Constitution.
In the meantime, Juan Antonio Ríos had become president and one of the principal leaders of the Radical Party. During the administration of colonel Carlos Ibáñez del Campo he was caught between his party's opposition to the government's dictatorial administration and his personal admiration for the government's results. As party president, he participated of the Thermal Congress (an unelected Congress convened by President Ibañez) as a senator for Arauco, Malleco and Cautín. After the fall of general Ibañez in 1931, Ríos was expelled from his party for his cooperation with the former dictatorship.
1932 was a very politically turbulent time for Ríos. First, he supported the Chilean coup of 1932, a successful coup that toppled President Juan Esteban Montero, and resulted in the proclamation of the Socialist Republic of Chile. Then he went on to become the Minister of the Interior when Carlos Dávila took over as head of state. In turn, after the resignation of Dávila three months later, general Bartolome Blanche became president, and Ríos became his Minister of Justice. Nonetheless, with the election of Arturo Alessandri in the presidential election of 1932 and the return to institutional normality, he was politically shunned.
Ríos run as an independent in the congressional election of 1933 and was elected as deputy for Arauco and Cañete. That was the beginning of his political comeback. In 1935 he was welcomed back into the Radical fold. In 1937, the Radical Party, the Socialist Party, the Communist Party, the Democratic Party and the Radical Socialist Party, as well as organizations such as the Confederación de Trabajadores de Chile (CTCH) trade-union, the Mapuche movement which unified itself in the Frente Único Araucano, and the feminist Movimiento Pro-Emancipación de las Mujeres de Chile (MEMCh) allied themselves in the Popular Front (Frente Popular), with Ríos becoming its first president. Nonetheless, Ríos was defeated in the internal presidential primaries by Pedro Aguirre Cerda, who got the nomination and then went on to win the presidential election of 1938.
During the Aguirre Cerda administration, he was president of Chile's largest bank, the state-owned Caja de Credito Hipotecario, which made mortgage loans to Chilean farmers. He also sought to increase his political influence inside his party. His main political rival was Gabriel González Videla, but soon he managed to have him named ambassador to France, leaving him free to pursue his own political advancement. At the time it was rumored that President Aguirre Cerda had also offered him an ambassadorial position, but that he had answered: ... tell the President that I thank him for his offer, but I am moving up, not down.
The left-wings' coalition was united by a common opponent, General Carlos Ibáñez del Campo. Ríos was a member of the conservative wing of the Radical Party and defeated Ibáñez in the 1942 election, portraying himself as a conservative anti-fascist candidate. Ibáñez had the support of Chile's Conservative party, Liberal Party, National Socialist party, Popular Socialist Vanguard and the majority of the independents. Ríos obtained 55,95% of the votes and took office on April 2, 1942.
Even though Ríos had been elected with the support of the Communist party, he refused the direct participation of this party in the government, thus earning their opposition. Ríos' option instead was to appoint "technical experts" and "personal friends" to cabinet and high-level government positions; this policy allowed him to include not only members of his own party, but also from the Conservative and Liberal opposition.
In 1943, Congress approved and Ríos signed the first constitutional reform to the 1925 constitution. This reform gave constitutional rank to the General Comptroller (Contraloría General de la República) and limited the power of the President with respect to public expenditures without congressional approval.
In 1944, the Radical Party itself presented to Ríos a serie of propositions which he deemed unacceptable. Those included breaking-off diplomatic relations with Francoist Spain — diplomatic and especially economic pressure had caused him to finally break off relations with the Axis Powers in January 1943 — the recognition of the USSR and a cabinet exclusively composed of Radicals. His refusal to implement the Radical Party's propositions, and the violent repression of riots that took place on Plaza Bulnes in Santiago, leading to several deaths, caused the resignation of all the Radical ministers, leaving the President without a party.
These internal divisions partly explain the right-wing parties success' during the 1945 legislative elections, which were a debacle for the Socialists and the Communists, who obtained close to no seats in Parliament. The Radicals themselves lost a number of seats. Finally, shortly after the end of the war, in October 1945, his entire cabinet resigned again, this time to protest a planned state visit he made to Washington D.C. to meet with President Harry S. Truman.
After his return from the United States, and faced with failing health, he finally gave in to the political pressure and appointed a cabinet made up exclusively of Radical party members. Soon after, he transferred his presidential powers to his minister of the Interior Alfredo Duhalde (January 17, 1946) and died a few months later, on June 27.
Thus in 1943, it was created the National Power Company (Empresa Nacional de Electricidad (Endesa)); in 1945, the National Oil Company (Empresa Nacional de Petróleos (ENAP)); and in 1946, the Pacific Steel Company (Compañía de Aceros del Pacífico (CAP)), which opened the Huachipato steelworks next to the port of Talcahuano.
Diplomatic and especially economic pressure from the United States finally caused him to break off relations with the Axis Powers on January 20, 1943. By doing so, he made Chile eligible for the Lend-Lease program, and obtained the necessary loans to help along the economic recovery. The close relations that emerged with the United States were, however, problematic for Ríos at home. Shortly after the war, in October 1945, his entire cabinet resigned in protest of the state visit he made to Washington D.C..