Manuel Ávila was born in the city of Teziutlán, a small town in Puebla, to middle-class parents. He had several siblings, among them sister María Jovita Ávila Camacho and several brothers. Two of his brothers, Maximino Ávila and Rafael Ávila Camacho both served as governors of Puebla. Ávila did not receive a university degree, although he studied at the National Preparatory School. He joined the army in 1914 as a 2nd lieutenant and reached the status of Colonel by 1920 and, in the same year, served as the Chief of Staff of the state of Michoacán under Lázaro Cárdenas, and became his close friend. In 1929, he fought under general Cárdenas against the Escobar Rebellion and, that same year, achieved the rank of Brigade General. He was married to Soledad Orozco García, who was born in Zapopan, Jalisco. Soledad Orozco was one of the Orozcos of the State of Jalisco. She was born in 1904 and died in 1996.
After his military service, Ávila entered the public arena in 1933–1934 as the Official Mayor of the Secretariat of National Defense, and became Secretary of National Defense in 1937. Two years later, he was elected president of Mexico, after being appointed to represent his party. Ávila won a controversial presidential election to the candidate of the Right-wing politics, Juan Andreu. The day of the election there was a lot of violence, and the electoral process was likely tainted with electoral fraud.
During his term, Ávila faced the difficulty of World War II. After two of Mexico's ships carrying oil were destroyed by German submarines in the Gulf of Mexico, Ávila declared war against the Axis powers on May 22, 1942. 15,000 Mexican soldiers fought in the war, on a variety of fronts, including an Airborne squadron, the 201st, to fight the Japanese in the Pacific. Furthermore, starting a period of friendship with the United States, Ávila cooperated in the war effort, providing his northern neighbour with 300,000 workers under the Bracero Program to replace some of the Americans who had left to fight in the war. Mexico also resumed diplomatic relations with the United Kingdom and Russia. In 1944, Mexico signed the United Nations Charter and the following year became the headquarters of the Interamerican Conference about War and Peace.
Domestically, Ávila protected the working class, creating social security in 1943 and working to reduce illiteracy. He continued land reform and declared a rent freeze to benefit low-income citizens. He also promoted election reform, creating new requirements that made it impossible for communists to run. He was also responsible, on January 18, 1946, for renaming what had been the Party of the Mexican Revolution (PRM) to the name it carries today, the Institutional Revolutionary Party (PRI).