John Sutton slotted Motherwell into an early lead but Manuel Pascali headed an equaliser before winning a soft penalty when he fell under an aerial challenge from Gavin Gunning.
Jamie Hamill converted the 43rd-minute spot-kick and Killie dominated the second half after Liam Kelly headed home at the near post six minutes after the break.
The victory moved Kilmarnock eight points above Motherwell with just three games left until the SPL split.
Motherwell, who were missing Stevie Hammell and the suspended Keith Lasley, were not helped by two injuries inside the first 10 minutes.
Francis Jeffers suffered an injury in the warm-up with Jamie Murphy restored to the starting line-up and Steven Saunders was stretchered off after twisting his ankle, with Ross Forbes coming on.
Both sides were guilty of some sloppy passing in the early stages but Motherwell made the better start and Sutton netted his fifth goal in four games in the 15th minute.
Tom Hateley's pass sent Chris Humphrey clear down the right and Sutton beat Pascali to the low cross to sidefoot the ball into the far corner from six yards.
Sutton came close to a second in the 20th minute when he glanced Steve Jennings' cross against the outside of the post from around the penalty spot.
Kilmarnock, for whom Anssi Jaakkola continued in goal with Cammy Bell again absent from the 18-man squad, levelled three minutes later.
The unmarked Kelly failed to connect with Alexei Eremenko's corner but the ball was only cleared as far as the Finn, who crossed for Pascali to head into the bottom corner from close range.
Kelly shot just over from 35 yards as Kilmarnock enjoyed a good spell and they took the lead in controversial fashion after Mike Tumilty blew his whistle when Pascali fell as he and Gavin Gunning jumped for a cross.
Tumilty was surrounded by Motherwell players but Hamill kept his nerve to slot the ball into the corner.
Gunning was booked for continuing his protests before team-mate Shaun Hutchinson followed into the book for a foul on William Gros, which sparked an angry reaction from the Killie striker and a mass confrontation.
Darren Randolph pushed wide David Mendes da Silva's powerful drive but he was picking the ball out of his goal after the resulting corner six minutes after the break.
The goalkeeper, who won a Republic of Ireland call-up this week, was beaten to Eremenko's near-post delivery by Kelly, who glanced a header inside the post.
Jonathan Page was soon taken off seconds after firing a shot out for a throw-in with Steve Jones coming on in left midfield and Gunning dropping back one.
Eremenko had the chance to kill the game off on the hour mark when Silva's inside pass found him in space 16 yards out but the Finland international could not keep his shot down.
Jennings shot straight at Jaakkola after a one-two with Sutton outside the box and then set up Murphy, who shot over under pressure.
Motherwell came closer when Craig Bryson cleared Gunning's header off the line following a Ross Forbes corner, but they were almost immediately caught out on the break.
Bryson set up Hamill but Randolph saved the right-back's low drive from 16 yards. Hamill soon repaid the favour with a brilliant cross, but Bryson headed straight at the keeper.
Motherwell's attempts to fight back were undermined by their inability to keep possession long enough and the introduction of Esteban Casagolda for substitute Forbes had little impact.
Killie finished well on top and Bryson hit the post from 20 yards before slicing wide from Hamill's cutback.
Randolph then made a double save from Silva and Hamill following good overlapping by Tim Clancy.
Jaakkola pushed over Hateley's late free-kick but Killie otherwise saw out the game comfortably.
Kilmarnock 3-1 Motherwell: Match Report - view commentary, squad, and statictics of the game as it happened.
Source: DSG
