The Mule uses his ability to conquer the Foundation (and carve his own empire out of nearby territory), sweep aside the remnants of the Galactic Empire centered around Neo-Trantor, and set up his own short-lived Galactic Empire — the "Union of Worlds", styling himself "First Citizen of the Union". The Mule based his rule on the planet Kalgan, which he obtained by mentally converting the warlord of Kalgan. After conquering the Foundation, he made Kalgan the capital of the Union. Leading up to, during, and for a good time after the Mule's conquest of the Foundation and its trade confederacy, no one ever actually saw the Mule or knew what he looked like.

The Mule established his empire incrementally, using past conquests to aid new ones: first by mentally converting a pirate band to his allegiance, then a whole planet, then the militarily powerful kingdom of Kalgan, then the Foundation (and the Imperial Remnant). The Foundation, after the death of the Empire, was the sole supplier of nuclear weaponry in the galaxy, and using this asset the Mule began rapidly conquering surrounding territories, all of which lacked nuclear power.

The Mule's conquest was amazingly fast: he defeated the Foundation and established the Union of Worlds after only five years. Then, just as suddenly, and seemingly randomly, the Mule stopped his advance and settled into a five year period of consolidation. This was actually because the Mule feared the Second Foundation, rumoured to be capable of defeating a mentalic individual like himself. However, the location of the Second Foundation was a total mystery. No one had ever heard anything other than the name, and besides rumours the popular sentiment was that there was no Second Foundation.

During this period of consolidation, the Mule launched repeated expeditions in search of the Second Foundation, which according to a hint by Hari Seldon existed "on the opposite side of the galaxy" from the First Foundation on Terminus. The last of these, led by Han Pritcher and Bail Channis, was successful, although not exactly in the sense the Mule had intended.

The Mule's name is a reference to the sterility of mules, since he too is genetically sterile. Without conceiving a child as a successor, the Mule's empire does not last long after his death.