Born in Tasmania, Syd Nicholls spent most of his youth in New Zealand. Leaving school early, he studied at the Royal Art Society and began selling cartoons to the International Socialist, the Bulletin and Direct Action during World War I. After one of his Direct Action cartoons 'prejudiced national recruiting', his editor was imprisoned and he found it hard to get work as in comics. For a period, he designed movie posters and studied design in the United States.

As art editor for the Evening News, Nicholls developed the comic strip 'Fatty Finn' and subsequently adventure strip 'Middy Malone' in 1928. He went to New York in 1930 trying unsuccessfully to sell 'Middy Malone'. In 1934 he teamed up with Stan Clements and launched what some consider to be Australia's first local comic, Fatty Finn's Weekly. In 1943 he produced The Phantom Pirate.

In 1946, Nicholl's established Fatty Finn Publications to publish a line of comics produced by Australian artists, including Fatty Finn's Comic, Middy Malone's Magazine and Cooee Comics.

Nicholls also illustrated several information books about ships.