The prolific Ayrshire outfit had claimed consecutive 3-0 away victories at both Hearts and St Johnstone, but St Mirren were the only team they had previously beaten at home in the Scottish Premier League this term back on September 11.
That all changed tonight as, after Ben Gordon had given them a 34th-minute lead with his first goal for the club, the home side upped a gear in the second-half to drive home their superiority and take the game away from Hamilton.
Conor Sammon led the way with a brace, first seizing on some slack Hamilton defending to net 52 seconds after the restart, before he headed in a second after 52 minutes for that now familiar 3-0 scoreline.
It was no surprise to see Kilmarnock put out an unchanged team, but Hamilton did make a change in attack, Nigel Hasselbaink restored to the starting line-up for the benched Marco Paixao.
Mehdi Taouil had the first effort of the game as the ball landed kindly for him from a Manuel Pascali free kick, but his driven effort from long range was held with relative ease by Tomas Cerny in the Hamilton goal.
Kilmarnock frontman Sammon turned Martin Canning brilliantly after 16 minutes, but again the eventual finish was disappointing, a weak hit straight at Cerny.
A dreadful Taouil pass straight to his opponent Dougie Imrie created the best of the early chances, as the midfielder put Hasselbaink through, but he blazed over the bar.
Hamilton were forced into a 24th-minute switch when Hasselbaink, suffering an apparent hamstring injury, limped off to be replaced by Damian Casalinuovo.
Sammon battled his way beyond Martin Canning after 29 minutes only for Cerny to dive to his feet and claim right on the edge of the penalty box amid Kilmarnock protests he had handled the ball outside of the area.
Liam Kelly collected the match's first caution for a foul on Paixao and from the resulting Hamilton free-kick, a fierce Imrie strike deflected wide off the Kilmarnock defensive wall.
The home team moved ahead in the 34th minute when Ben Gordon, on loan at Kilmarnock from Chelsea, stepped inside a Canning challenge and curled the ball expertly past Cerny.
Hamilton should have levelled when after fine set-up play from Imrie on the left, Casalinuovo slid in at the far post, but could only direct his effort over the bar.
Kilmarnock continued to press before the interval and came close to a second goal when Alexei Eremenko sent a swerving shot just over the bar.
Kilmarnock doubled their lead within a minute of the restart when Mark McLaughlin and Canning both failed to head clear, allowing Sammon in behind them to score.
Eremenko was his usual confident self in midfield and the Finn almost surprised Cerny with an audacious long-range chip that only just cleared the crossbar with the goalkeeper backtracking.
It was 3-0 to Kilmarnock in the 52nd minute when Bryson's searching cross from the left found the leaping Sammon and his firm header beat the diving Cerny.
Sammon was seeking a hat-trick now and might have got it on the hour mark when Hamilton were unable to deal with a Taouil cross, but the striker shot wide this time.
Kilmarnock were playing some fluent football now and might have claimed a fourth goal had Taouil been more precise with his volleyed finish after a move he started himself in his own half.
With victory seemingly not in doubt, Kilmarnock began to make some changes, withdrawing Frazer Wright and Eremenko with the weekend trip to Dundee United in mind.
Jamie Hamill advanced from right-back to send a spinning shot over the reach of Cerny and onto the top of the crossbar in the 77th minute as the home team remained dominant.