Smyth joined the Royal Navy and during the Napoleonic wars he served in the Mediterranean, eventually achieving the rank of Admiral. He married Annarella Warrington in 1815. During a hydrographic survey in 1817 he met the Italian astronomer Giuseppe Piazzi in Palermo, Sicily, and visited his observatory; this sparked his interest in astronomy and in 1825 he retired from the Navy to establish a private observatory in Bedford, England, equipped with a 5.9-inch refractor telescope. He used this instrument to observe a variety of deep sky objects over the course of the 1830s, including double stars, star clusters and nebulae. He published his observations in 1844 in the Cycle of Celestial Objects, which earned him the gold medal of the Royal Astronomical Society and also the presidency of the society. The first volume of this work was on general astronomy, but the second volume became known as the Bedford Catalogue and contained Smyth's observations of 1604 double stars and nebulae. It served as a standard reference work for many years afterward; no astronomer had previously made as extensive a catalogue of dim objects such as this.
Having completed his observations, Smyth retired to Cardiff in 1839. His observatory was dismantled and the telescope was sold to Dr. John Lee and re-erected in a new observatory of his own design at Hartwell House. Smyth still had the opportunity to use it since his residence at St. John's Lodge was not far from its new location, and did a large number of additional astronomical observations from 1839 to 1859. The present whereabouts of the telescope are unknown.
Smyth suffered a heart attack in early September, 1865, and at first seemed to recover. On September 8 he showed the planet Jupiter to his young grandson, Arthur Smyth Fower, through a telescope. A few hours later in the early morning of September 9, at age 78, he died. He was buried in the churchyard at Stone near Aylesbury.
See also Charles Piazzi Smyth (son)