A goalless draw looked on the cards until Dougie Imrie bundled home 18 minutes from time, before Flavio Paixao added a stunning second and Joel Thomas wrapped up a thumping win with his third goal in two games.
Killie never seriously threatened Tomas Cerny's goal in what was both sides' first post-split fixture and the defeat left them in the thick of the relegation battle.
In-form Hamilton kept faith with the starting XI that thrashed Hibernian 4-1 last weekend as they eyed the win that would guarantee a third successive season of SPL football.
Struggling Killie made four changes, recalling fit-again captain Craig Bryson, Mark Burchill, Jamie Hamill and Liam Kelly.
Accies had hauled themselves clear of danger thanks to a run of one defeat in eight games, including a 2-1 victory at Rugby Park last month.
In stark contrast, their opponents boasted just one win and seven defeats in all competitions.
They also had the worst away goal haul in British league football, having scored just four times on their travels this season.
Accies were having no problem finding the net and Cameron Bell did brilliantly to claw Grant Evans' header behind from Imrie's cross inside five minutes.
Kelly picked up a ninth-minute booking after chopping down the latter, while neat interpassing just after the quarter-hour ended with James McArthur firing left-footed straight at the goalkeeper from 20 yards.
Mickael Antoine-Curier was then involved at either end midway through the half, blocking the ball on his own line after Hamilton failed to deal with a corner before being gifted possession by Manuel Pascali, bearing down on goal and shooting too close to Bell.
Killie enjoyed a brief spell on top but they were living up to their reputation of being shot-shy on their travels.
Accies regained control but, in fairness, were also unable to test the goalkeeper.
Hamill picked up the visitors' second booking five minutes before the break for a lunging tackle on Flavio Paixao.
The resulting free-kick and two corners all went begging as the first half ended goalless.
Accies withdrew Evans for Marco Paixao during the interval.
Less than four minutes after the restart, Antoine-Curier and Mark McLaughlin were both appealing for what they appeared to think was handball on the line from Garry Hay after a Flavio Paixao corner.
Both sides had cranked up the aggression but although tackles were beginning to fly in, referee Dougie McDonald was unmoved.
He had a big call to make just past the hour mark when Antoine-Curier got the wrong side of Tim Clancy and went down under pressure from the defender.
It looked a decent penalty shout but McDonald decided to book the striker for diving instead.
Hostilities briefly ceased when Cerny required treatment just outside his own penalty area before Antoine-Curier had a golden chance to put Hamilton ahead in the 68th minute.
Hamill's clearance careered off Marco Paixao straight to the striker, whose shot was turned behind superbly by Bell.
Killie responded by replacing strike force Allan Russell and Burchill with Chris Maguire and Danny Invincibile.
But they fell behind almost immediately, Bell failing to claim a Marco Paixao corner and Imrie sweeping home from point-blank range.
Hamilton then brought on Thomas for Antoine-Curier before McArthur was booked for a foul on Garry Hay.
The some side soon had a second goal and it was as spectacular as their opener was scrappy.
Imrie's 77th-minute cross was headed clear by Pascali but the ball was met full on the volley by Flavio Paixao and rocketed into the bottom corner.
Killie looked beaten, while their opponent were now full of confidence, though they had to replace Cerny with Sean Murdoch soon after.
Their afternoon was capped three minutes from time when Thomas made it 3-0, outmuscling Simon Ford before rifling a left-foot finish into the bottom corner.
Killie's misery was complete when Clancy was booked in stoppage-time for clattering into Flavio Paixao.