Paoli was one of nine siblings born and raised in the family farm in the town of Lares, a town which is historically known for El Grito de Lares, Puerto Rico's first rebellion for independence.

His mother, whom he considered his greatest inspiration, died in 1930, when he was 15 years old. The death of his mother compelled him to write his first collection of poems, titled Signario de lágrimas, which was published in 1931. Paoli received his primary and secondary education in his hometown. In high school he dedicated most of his time to reading classical literature. It was during his youth that he met Pedro Albizu Campos and became inspired to join the Puerto Rican Nationalist Party in its struggle for Puerto Rico's independence.

In 1933, Paoli met fourteen year old Lolita Lebrón, during the celebration of her baptism into the Catholic faith. Soon, Paoli became Lebron's first boyfriend and they would often write letters to each other where they exchanged the poetry that they wrote. Paolí's family opposed their relationship because they considered Lebrón a jíbara (peasant). Her father also opposed this relationship and ordered her to stop writing to Paoli. However, they both continued to write to each other until he moved to San Juan to continue his education.

Matos Paoli enrolled at the Polytechnical School of the University of Puerto Rico and earned his Bachelor's degree in education with a major in Spanish. Lebrón, who became a nationalist herself and led the 1954 attack against the United States House of Representatives, moved to San Juan, where she studied sewing and where she continued her romantic relationship with Paoli. The relationship was ended when Paoli continued his postgraduate studies in the UPR and moved to Paris, France for a year to study comparative literature at the "La Sorbonne". In 1937, he published his second collection of poems titled Cardo labriego. During this timeframe, he met Isabel Freire Meléndez, a fellow independence advocate who in 1942 became his wife. After he earned his Master's degree in Spanish literature, he returned to Puerto Rico and in 1943 began a professorship in his Alma Mater in the Humanities Department. He also became involved in spiritualism and founded a spiritualist center called "Luz Y Progreso" (Light and Progress).

Paoli's political activities and believes influenced his creativity in regard to his poetic works. On June 11, 1948, the United States appointed Governor of Puerto Rico, Jesús T. Piñero, signed the infamous "Ley de la Mordaza" (Gag Law) or Law 53 as it was officially known, passed by the Puerto Rican legislature which made it illegal to display the Puerto Rican Flag, sing a patriotic song, talk of independence and to fight for the liberation of the island. It resembled the anti-Communist Smith Law passed in the United States. In 1949, the Nationalist Party held an assembly in the town of Arecibo and named Paoli Secretary General of the party. Some of his responsibilities as Secretary General of the party included the presentation of patriotic speeches.

In September 1950, Paoli traveled to the towns of Cabo Rojo, Santurce, Guánica and Lares in participation of nationalist activities. On October 30, the nationalists staged uprisings in the towns of Ponce, Mayagüez, Naranjito, Arecibo, Utuado (Utuado Uprising), San Juan (Nationalist attack of San Juan), and Jayuya (Jayuya Uprising). On November 2, 1950, the police arrived at Paoli's home in Río Piedras and searched for guns and explosives, however the only thing that they found was a Puerto Rican flag. He was arrested and accused of violating the "Ley de la Mordaza" (Gag Law). The evidence used against him was that he had a Puerto Rican Flag in his residence and that he had made four speeches in favor of Puerto Rico's independence. Paoli was fired from his professorship at the UPR and was sentenced to a twenty year prison term, the sentence was later reduced to ten. In jail, he shared his cell with Albizu Campos. Campos suffered from ulceration's on his legs and body caused by radiation and Paolí tended to his needs.

In prison Paoli edited a newspaper which included news of political prisoners, poems, patriotic songs and drawings. In 1951, he published a collection of poems in a book which he titled Luz de los héroes (The Light of Heroes) In his poems he spoke about the reality of the Puerto Rican struggle for freedom. Paoli was released on January 16, 1952, on probation. During his confinement he suffered from hallucinations which resulted in a mental breakdown and he was sent to a Psychiatric hospital. After his recovery, he wrote Canto a Puerto Rico (I sing to Puerto Rico), and he once more became involved with the world of spiritual mysticism and Christianity.

After he recovered, he continued to write poetry. In his poems he covered various aspects of human existence such as religion, mystic and spiritual experiences, love, death, solitude, social justice, suffering, freedom, the landscape, and his fellow Puerto Ricans.

On March 1, 1954, Lolita Lebrón together with three other members of the Nationalist Party reached the visitor's gallery above the chamber in the House of Representatives in Washington, D.C.. Lebron stood up and shouted "¡Viva Puerto Rico Libre!" ("Long live a Free Puerto Rico!") and unfurled the flag of Puerto Rico. Subsequently the group opened fire with automatic pistols. The government ordered the arrest of the members of the Nationalist Party including Paoli, who was not involved in the incident, was sent to the local prison in Río Piedras and jailed. Paoli began a hunger strike because he and the other nationalists were not allowed to receive visitors. On May 26, 1955, after serving ten months in jail, Paoli was in poor physical health and was released upon a pardon granted by Puerto Rican Governor Luis Muñoz Marín.

Paoli was named resident poet of University of Puerto Rico and served as lecturer. In 1977, the Department of Hispanic Studies at the UPR campus in Mayagüez nominated him for the Nobel Prize in literature in recognition of his substantial contribution to world literature. His critics consider his books rooted in three major literary movements in Latin America: Romanticism, Modernism, and Postmodernism. Among his many published works are the following:

• Canto a Puerto Rico (1952) "I sing to Puerto Rico",
• Luz de los héroes (1954) "Light of Heroes",
• Criatura de rocío (1958),
• Canto a la locura (1962) "Song to the madness",
• El viento y la paloma (1969) "The Wind and the Pigeon",
• Cancionera (1970) "Song Book",
• La marea sube (1971) "The Raising Waves",
• Cancionero II (1972) "Song Book Pt.2",
• Rostro en la estela (1973) "A Face in the Star",
• Isla para los niños (1981) "Island for Children",
• Hacia el hondo vuelo (1983) "Towards the Deep Flight",
• Decimario de la Virgen (1990)

Note: You may listen to Francisco Matos Paoli's ""Invocación a la Patria"" as interpreted in song by grupo Otoqui [1]

Paoli and Lebron remained lifelong friends and he wrote the forward to one of her books of poems. In July 1982, Paoli was selected as one of fifty poets to attend the Sixth World Congress of Poets held in Madrid, Spain. He also attended, by invitation, the eighth World Congress of Poets in Athens, Greece in 1985. Among the magazines which published his essays were Asomante, Puerto Rico Ilustrado, and Alma Latina. In 1989, the Manati Foundation of Art and Culture of the town of Manati, dedicated their annual "Juegos Florales" (poetry pageants) to Paolí.

Paoli lived with his wife Isabel Freire Meléndez de Paoli (1915—2004), herself a renowned educator and journalist, in San Juan. He became ill and was hospitalized at the Hospital del Maestro in Hato Rey where he died on July 10, 2000.