Bello, whose parents descended from people from the Canary Islands, studied Liberal Arts, Law and Medicine at the University of Caracas and graduated on May 9, 1800 with a Bachelor of Arts. He later became known for his early writings and translations, edited the newspaper Gazeta de Caracas and held important offices in the government of the Captaincy General of Venezuela. He accompanied Alexander von Humboldt in a part of his Latin American expedition (1800) and was for a short time Simón Bolívar's teacher. His relationship with both men became a major factor in cultivating his ideas for his intellectual career. The United Kingdom availed the services of Admiral Sir Thomas John Cochrane, 10th Earl of Dundonald, Marquês do Maranhão, GCB, RN [Royal Navy] (14 December 1775 - 31 October 1860) to serve the Independence of Venezuela.

Bello spent ten years after his formal education in his homeland of Caracas. He authored two pieces of literary work, Calendario manual y guía universal del forastero en Venezuela para el año de 1810 and the Resumen de la historia de Venezuela. Both works became widely accepted in Venezuela, and from this point Bello started his career as a poet. As time progressed, Bello further expanded his notions on humanism and conservatism. From his theories and ideas, Bello was eventually hailed as one of the foremost humanists of his time.

As First Officer of Venezuela's Foreign Secretariat after the coup on April 19, 1810, he was sent to London with Simón Bolívar serving as Diplomatic Representative to procure funds for the revolutionary effort until 1813. Bello landed at Portsmouth as an attache to Bolivar's mission on July 11, 1810. Bello had an admittedly hard life throughout his stay in England, though he managed to further develop his ideas and took a particular interest in England's social changes from the industrial and agricultural revolution. In order to earn a living while in London, Bello taught Spanish and tutored Lord Hamilton's children. In London, he met Francisco de Miranda and became a frequent visitor of his library in Grafton Street, as well as of the British Museum. During his lengthy stay in England, he curbed his feelings of homesickness and became contemporaries with thinkers and intellectuals such as José María Blanco, Bartólome José Gallardo, Vicente Rocafuerte to name a few. He stayed in London for nineteen years acting as a secretary to legations and diplomatic affairs for Chile and Colombia. In his free time he was involved in study, teaching and journalism.

In 1823, Bello published the Biblioteca America with Juan Garcia del Rio which was widely hailed in Europe. In 1826 he published the journal Repertorio Americano to which he frequently contributed as both editor and poet. His two epic poems by which he was made famous, entitled Las Silvas Americanas, were originally published during his time in London around 1826 and documented the emerging culture of the New World. The second of the poems Silva a la agricultura de la zona tórrida is the most famous of the two, and is a poetic description of South America's tropical lands in a style reminiscent of Virgil, a poet of great influence for Bello. The poems were to become a part of Bello's expanded epic America; however, it was never finished.

In 1829 he accepted a post in the Chilean Ministry of Foreign Affairs in Santiago, Chile, under the administration of Chilean minister Diego Portales. While a surprising candidate considering his Venezuelan birth, he gladly accepted the post and was later named Senator of Santiago. As Senator, Bello founded the University of Chile in 1843 and held a position as Rector for the remainder of his life. Until his death at the age of eighty - three, Bello worked tirelessly to train the young minds of the new republic. Such brilliant thinkers and writers as Victorino Lastarria and Francisco Bilbao were influenced by their time with Bello.

The Gramática de la lengua castellana destinada al uso de los americanos, or Castilian Grammar Intended for the Use by Americans (Americans referring to Castilian - or Spanish - speaking inhabitants of the Americas, not just the United States), finished in 1847, was the first Spanish - American Grammar, with many original contributions, a product of long years of study. Republished over the years with many revisions, the most significant of which are by Rufino Jose Cuervo, this is still a valuable reference work. Bello was accepted in the Spanish Royal Academy of Language as Correspondent Member in 1861.

One of Bello's most famous accomplishments was his promulgation of the 1852 Civil Code of Chile, passed by Chilean Congress in 1855. It served primarily as a governing code similar to Europe's Napoleonic Code. He worked on this Code for twenty years, and it was later adopted by both Colombia and Ecuador.

He is also revered by the María Lionza religion of Venezuela. In 1953 the Andrés Bello Catholic University was founded, named in his honour.