Mickael Antoine-Curier and Simon Mensing netted within five minutes of each other midway through the first half as Accies moved eight points away from the bottom of the SPL.
The Lanarkshire side missed several chances to put the game out of sight before Chris Maguire pulled one back, but they survived the remaining 13 minutes without serious danger.
Killie recalled Kevin Kyle, Chris Maguire and Manuel Pascali after all were unavailable for their Scottish Cup defeat, but their losing run stretched to five games after they failed to cope with Hamilton's movement for the majority of the game.
Hamilton settled almost immediately, although midfielder James McArthur had an early escape when the ball hit his hand after he miscontrolled it inside the box.
Cammy Bell then had to look lively to save Brian Easton's deflected shot after the Accies wing-back broke with purpose.
Tomas Cerny was soon called into action to tip over a 20-yard effort from Kyle, who then looped a header over from Craig Bryson's free-kick.
But Hamilton were growing in confidence and took the lead in the 21st minute when Antoine-Curier converted an easy chance for his second goal in as many games.
Mensing released James Wesolowski in the right channel and the Australian showed a good turn of pace to get to the byline before his deflected cross fell perfectly for Antoine-Curier to bundle home at the far post.
Billy Reid's men doubled their lead when Mensing planted a firm header into the corner from Imrie's left-wing cross.
Killie were staring defeat in the face when Rob Kiernan, in for the suspended Frazer Wright, took a fresh-air swipe on the edge of his box but he recovered to make a crucial sliding challenge on Antoine-Curier.
Accies had a real verve to their play and could have added more before the break. Wesolowski and Easton both had shots blocked inside the box, the latter denied by a flying intervention by Pascali after Imrie claimed for a penalty following Liam Kelly's challenge.
Accies came even closer from Flavio Paixao's corner, with James Fowler clearing Mensing's header off the line. Craig Bryson was booked for a dive in the box as Killie struggled to get back in the game.
Kilmarnock's attacking play showed no signs of immediate improvement in the second half, even after Jimmy Calderwood brought on two more strikers in Mark Burchill and Allan Russell 10 minutes in.
Imrie soon missed a glorious chance when he curled wide from 12 yards after Antoine-Curier's cutback.
Kilmarnock finally began pushing Hamilton back midway through the half but were still lacking a cutting edge.
However, they got a lifeline after Marco Paixao, who had come off the bench moments earlier, gifted possession to Kelly midway inside his own half.
Kelly fed Maguire in the right channel and the on-loan Aberdeen striker fired a swerving shot inside Cerny's near post.
Accies defender Mark McLaughlin grabbed hold of Paixao as he remonstrated with the substitute but his determination was soon put to positive effect as Hamilton soaked up some late pressure to stretch their unbeaten run to five matches.