Frederick's first commission, for Isambard Brunel, was six watercolour paintings of the Rotherhithe Tunnel. Four of these were exhibited at the Royal Academy when Frederick was 16. His first oil won a Society of Arts silver medal. He exhibited work at the Royal Academy 27 times between 1838 and 1859. He was elected Associate of the Royal Academy in 1852.
Goodall visited Egypt in 1858 and again in 1870, both times travelling and camping with Bedouin tribesmen. In order to provide authentic detail to his paintings, Goodall brought back sheep and goats from Egypt. The Eyptian theme was prominent in his work, with 170 paintings being exhibited at the Royal Academy over 46 years.
Goodall's work received high praise and acclaim from critics and artists alike and he earned a fortune from his paintings. He had a home built at Grim's Dyke, Harrow Weald, where he would entertain elaborate guests such as the Prince of Wales (later Edward VII). Frederick's brother, Edward Angelo Goodall (1819–1908) was also a highly gifted artist who exhibited at the RA from 1846 to 1853. A specialist in watercolours, he was invited to join the RWS (Royal Watercolour Society) in 1856 and exhibited 328 pictures at its exhibitions. It was Edward who had the distressing task of arranging the sale of his brother's pictures and effects when he was declared bankrupt in 1902. His other brother Walter Goodall was also a notable watercolour artist.