He was the son of a vicar who became a school master in his mid-twenties. After writing freelance articles in his spare time, he joined a newspaper for a short spell, then authored a series of secular pamphlets including Ananias, The Atheist's God: For the Attention of Charles Bradlaugh. After the success of Admiral Philip H. Colomb's The Great War of 1892 (itself a version of the more famous The Battle of Dorking), Griffith, then on the staff of Pearson's Magazine, submitted a synopsis for a story entitled The Angel of the Revolution. It remains his best and most famous work. It was the first synthesis of the 'marvel' tale epitomised by Jules Verne, featuring futuristic flying machines, compressed air guns and spectacular aereal combat, the 'future war' tales of George Chesney and his imitators and the political utopianism of William Morris's News from Nowhere. He wrote a sequel, serialised as The Syren of the Skies in the magazine and published as a novel under the title of its main character, Olga Romanoff.

Although somewhat overshadowed by H. G. Wells, Griffith's epic fantasies of romantic anarchists in a future world of war dominated by airship battlefleets and grandiose engineering provided a template for steampunk novels a century before the term was coined. The influence of books such as The Angel of the Revolution and the character of Olga Romanoff on British fantasy writer Michael Moorcock is striking. The concept of revolutionaries imposing "a 'pax aeronautica' over the earth", at the center of Angel of the Revolution, was taken up by Wells many years later, in The Shape of Things to Come. Wells himself once wrote that Griffith's Outlaws of the Air was an "aeronautical masterpiece."

Though a less accomplished writer than Sir Arthur Conan Doyle, Rudyard Kipling or H.G. Wells, his novels were extremely popular in their day, seeing many printings, and foreshadowed World War I and the Russian Revolution and the concepts of the air to surface missile and VTOL aircraft. He wrote several tales of adventure set on contemporary earth, while The Outlaws of the Air depicted a future of aerial warfare and the creation of a Pacific island utopia. Sam Moskowitz described him as "undeniably the most popular science fiction writer in England between 1893 and 1895."

His science fiction depicted grand and unlikely voyages through our solar system in the spirit of Wells or Jules Verne, though his explorers donned space suits remarkably prescient in their design. Honeymoon in Space saw his newly married adventurers exploring planets in different stages of geological and Darwinian evolution on an educational odyssey which drew heavily on earlier cosmic voyages by Camille Flammarion, W. S. Lach-Szyrma, and Edgar Fawcett. Its illustrations by Stanley Wood have proved more significant, providing the first depictions of slender, super intelligent aliens with large, bald heads — the archetype of the famous Greys of modern science fiction. His short story The Great Crellin Comet, published in 1897, was the first story to not only include a ten second countdown for a space launch, but also the first story to suggest that a cometary collision with the earth could be stopped by human intervention.

As an explorer of the real world he shattered the existing record for voyaging around the world, completing his journey in just 65 days, and helped discover the source of the Amazon river. This was documented in Pearson's Weekly newspaper before being published as a book Around the World in 65 Days in 2009. He died of cirrhosis of the liver, at the age of 48, in 1906. His son was famed aeronautical genius Alan Arnold Griffith, who was the inventor of the Avon jet engine.

In 2006 Apogee Books released The World Peril of 1910 as part of its series of classic science fiction.

In 2008 Apogee released Around the World in 65 Days, an anthology of travel writing. The book collects Griffith's world travels, including one trip around the world done in a record-breaking 65 days. In addition, many of Griffith's other adventures are included. His trip to South America is recounted in "A Railway Beyond the Clouds", "A Ride to the City of the Sun", "A Paradise of Tomorrow", "The Most Majestic Mountain", and "Los Medanos". His travels of North America in "The Snake-Dancers of Arizona" are somehow even more exotic. Griffith claims to have made the first intentional flight across the English Channel in "To France by Air". In "When will the 20th Century Begin?", Griffith discusses the intricacies of time zones, something with which he has quite a lot of practice.

In 2009, Leonaur Press released The Angel of the Revolution and Olga Romanoff as a two-volume set entitled Empire of the Air in both hardback and paperback.