It was written as a sequel to Fighters from Mars, an unauthorized and heavily altered version of H. G. Wells's 1897 story The War of the Worlds.

Set after the devastating Martian attack in the previous story, the novel depicts Edison leading a group of scientists to develop ships and weapons, including a disintegration ray, for the defence of Earth.

Edison and company fight the aliens in space and on Mars, eventually causing a flood that defeats the enemy and forces an end to hostilities.

[1] The book is set following the abortive Martian attack depicted in Fighters from Mars, much more devastating and global than in H. G. Wells' The War of the Worlds, though in both works the onslaught is thwarted when the aliens die from bacterial illness.

Determining that the Martians will inevitably return, Earth's leaders, including U.S. President William McKinley, Queen Victoria, Kaiser Wilhelm II, and Emperor Mutsuhito, unite the world against the common threat and plan an attack on Mars.

American inventor Thomas Edison leads a group of scientists studying derelict Martian equipment; they are able to develop an anti-gravity device powered by electric repulsion as well as a disintegration ray.

Aina advises Edison that meeting the Martians in battle would be fruitless, and that they should instead attack the dams that channel water from the polar ice.

[4] Edward Guimont has argued that Edison's Conquest of Mars was an influence on author H. P. Lovecraft's Cthulhu Mythos, particular with its use of the ancient alien tropes of massive alien-built ruins.