Nuclear fusion, for the less scientifically-minded, is the process of forming a new atom by combining two or more smaller atoms. Because atoms have forces which act to prevent them from normally getting so close, this is a very difficult task. However, it is precisely because of this fact that so much energy is released when the atoms are joined. The exposive result of nuclear fusion is known as a fusion reaction.
Because of the difficulties in forcing atoms to join, much energy is required simply to start the reaction. Once it is started, however, far more energy is released than was used up. Still, fusion reactions are easier to initiate using certain atoms, which is why Megatron's cannon cannot simply use atoms from the surrounding air. One such atom, deuterium, is found in relatively abundant supplies within the Earth's oceans. It is also possible that Megatron's fusion cannon is able to capture some of the energy of each fusion reaction for use in initiating the next one. In this way, his cannon could hypothetically fire forever, assuming he had a continuous supply of fusionable atoms and no damage occurs to the weapon.
Despite several scenes in the comic depicting anti-recoil energy release coming out from the back of the fusion cannon, this seems to be the exception rather than the rule, and can thus be considered non-canon. Most artists depict the fusion cannon such that no energy is released backwards upon firing, a situation which would result in enormous recoil (as was shown in the cartoon when Brawn attempted to fire it).
So how powerful is the fusion cannon? First, let us view evidence from the cartoon. Gears was captured when Megatron blasted a hole beneath his feet with a single shot; the hole was deeper than Gears was tall. Megatron decimated large portions of one of Lookout Mountain's cliffs with several shots. Ironhide was presumably killed with a shot to the head with the cannon. The fusion cannon was unable to damage Autobot City's armored walls, yet the Insecticons were capable of chewing through them, and Devastator could tear them apart with his hands.
The comic also had several examples of the fusion cannon's use. Optimus Prime was shot by Megatron and was rendered helpless, yet was not otherwise visibly damaged by the blast. Swoop was hit by the cannon, and while he was knocked unconscious momentarily, he too appeared to be unharmed. Shockwave was thrown though a volcano wall, and several hundred meters by a close-range fusion cannon blast. He too was apparently undamaged. The cannon was unable to penetrate Omega Supreme's wing-shields. In the UK comic, a single blast knocked Blades unconscious. Once again, no damage from the cannon could be seen, and the Protectobot was able to fly shortly after. It has been shown time and time again that the cannon is capable of destroying nearly anything human-made (ie. Destro's castle, an Action Force Dragonfly). In what is arguably the fusion cannon's most impressive showing in the comic continuity, a single shot from the cannon was able to bring down a fully operational Predaking.
In the comic continuity, Megatron has now replaced his fusion cannon with a hyper-velocity rail gun, supplied by Cobra. This weapon is mounted on his right shoulder, and appears to have more penetrative power than his fusion cannon, at the cost of ammunition consumption. Megatron appears to have no objections to this new weapon.
In the realities in which Megatron became Galvatron, Unicron has for some reason replaced the fusion cannon with what is supposedly a laser. This would seem like a step backward, until one considers that Galvatron was, at the time, being powered continuously by Unicron. In such a scenario, a laser, with its complete non-reliance on supplies, would outperform even a fusion cannon.