Klitschko, who earned an 11th-round stoppage win over the American four years ago, was dragged out of his usual defensive fortress almost immediately but recovered from a shaky opening pair of rounds to take full control.
A low guard from the American was punished in round five with a stinging right hand, and though Thompson beat the count he was unable to do so in the sixth as 'Dr. Steelhammer' struck again to keep hold of his WBA, IBF, WBO, IBO and The Ring heavyweight straps.
Meanwhile, potential future Klitschko challenger Tyson Fury cruised to a one-sided success over Vinny Maddalone to claim the WBO Intercontinental title with a referee stoppage in the middle of round five.
Fury wore his American adversary down with his jab from the opening bell, cutting him in round four before an official intervention to prevent any further abuse in what proved to be a mis-match in Clevedon.
Kell Brook, on the other hand, had to graft a little harder for success in a bloody and compelling majority decision victory in his home town of Sheffield over Carson Jones in a welterweight World title contention eliminator.
After showing great style to dominate the early rounds, Brook was dragged into a war of attrition by his rugged opponent and appeared to be in deep trouble at the half-way stage after sustaining what may well be a broken nose, leaving 'The Special One' a bloodied mess.
But the undefeated local lad showed a whole new side from there, catching a second wind to rally in the championship rounds and put himself out of reach in the eyes of two of the three judges, with the third ruling the bout a draw.
In other notable results, Gavin Rees retained his British and European lightweight titles with a round-nine stoppage against a physically-tough but technically-outgunned Derry Mathews, while Grzegorz Proska regained his European middleweight belt in another rematch, defeating Kerry Hope in the eighth.
Chris Eubank Jnr also continued his promising career in successful fashion under the watchful eye of his former World super-middleweight champion father, earning the referee's decision after six exciting rounds against Terry Caruthers, while Lee Haskins captured the European bantamweight title with a unanimous decision victory over Stuart Hall.