Francis was one of twelve children born to Mang and Frances Schwarzenbach Seelos; he was named for Saint Francis Xavier. His father was a textile merchant who became parish sacristan. Francis was Confirmed on 3 September 1828, and made his first Communion on 2 April 1830. The boy wanted to be a priest from an early age, and often claimed he would be another Francis Xavier. He completed his basic studies in Füssen, Germany, and graduated from the Institute of Saint Stephen in Augsburg, Germany in 1839. Received a degree in philosophy and theology from the University of Munich, and entered the Saint Jerome seminary in Dillingen an der Donau, Germany on 19 September 1842. Francis became familiar with the Congregation of the Most Holy Redeemer, and their mission to work with the poorest, the abandoned, and immigrants. He joined on 22 November 1842. Feeling a call to minister to German immigrants to America, he left the seminary on 9 December 1842, sailed for the America on 17 March 1843, and arrived in New York on 20 April. He was ordained in the Redemptorist Church of Saint James in Baltimore, Maryland on 22 December 1844.
He worked nine years at Saint Philomena parish in Pittsburgh, Pennsylvania, six of those years as assistant pastor to, and spiritual student of Saint John Neumann, and the other three as superior and novice master of his Redemptorist community. Faithful to the Redemptorist teachings, he led a simple life, preached a simple message, and was always available to those in need. His sermons drew crowds from neighboring towns, there were lines outside his confessional, and he never tired of working with children. He heard Confessions in English, German, and French, from black and white penitents and anyone else with a burden. He was transferred to parish ministries in Baltimore in 1854, Cumberland, Maryland in 1857, and Annapolis, Maryland in 1862. He was proposed as bishop of Pittsburgh in 1860, but he begged to be excused "from this act of God", and his desire was granted by Pope Pius IX.
In 1863, during the American Civil War, all men were obliged to be available for active military duty. Seelos, as Superior of the Redemptorist Seminary, met with President Abraham Lincoln, and obtained an agreement not to send seminarians to the front. Seelos soon after lost his position as Prefect of Students for being "too lenient".
From 1863 to 1866 he lived as an itinerant mission preacher in both English and German in Connecticut, Illinois, Michigan, Missouri, New Jersey, New York, Ohio, Pennsylvania, Rhode Island, and Wisconsin. Hearing of an influx of German immigrants to New Orleans, Louisiana, he pastored a Redemptorist church there beginning in 1866. He worked with yellow fever victims until he was taken by the illness the next year. Yellow fever claimed his life on 4 October 1867 in New Orleans, Louisiana. He is remembered on October 5.