Conor Sammon gave Killie the lead after four minutes but a lob from Phil McGuire brought the home side level.
The turning point came just before half-time when Andy Barrowman won a penalty when he was tripped in the box by Craig Bryson.
Despite protests from the visitors that the Caley striker had embellished his fall, Barrowman converted the spot-kick with aplomb.
James Fowler was sent off for Kilmarnock before Ian Black headed home a third for the Highlanders.
Barrowman returned to the starting line up for Inverness after his midweek suspension for Caley's Co-operative Insurance Cup win over Morton. Kilmarnock named the same starting XI that scored four goals in the opening 33 minutes to knock Aberdeen out of the same competition in midweek.
The game was only four minutes old when Inverness gifted their visitors an early lead. Michael Fraser left his goal unguarded when he came out to gather a Jamie Hamill free-kick and the ball fell to Simon Ford, whose shot deflected kindly into the path of Sammon for the easiest of finishes.
The former Derry City player should have grabbed his second a couple of minutes later when Mehdi Taouil crossed but the striker could not keep his volleyed effort down.
The home side could have got back on level terms in the 14th minute but Roy McBain failed to find the target with an ambitious lob after good work by Dougie Imrie and Barrowman.
Killie keeper Alan Combe was then deceived by a deep corner from Iain Vigurs but Sammon came to his rescue when he headed Barrowman's effort off the line.
Inverness did get back level soon after when Kilmarnock failed to deal with an Imrie free-kick and the ball dropped to McGuire, who gave Combe no chance with a left foot lob.
Combe prevented the home side taking the lead with a fine save from an Ian Black shot from the edge of the box.
Black had another thunderous effort tipped over the bar by Combe as the home side started to get the better of their opponents.
A superb ball by Vigurs released Imrie and he crossed into the danger area and only great defending from Hamill prevented Barrowman getting Caley's second.
The hosts were temporarily down to 10 men when Imrie required treatment for a knock in the face after an accidental collision with Manuel Pascali.
But they took the lead when Barrowman went on a mazy run in the box before being brought down by Bryson.
Barrowman was not put off by the Killie protests he had dived and stepped up to fire the ball high into the net.
Fowler and Combe were booked for their complaints, while David Fernandez was fortunate to go unpunished after pushing Barrowman just before the striker converted the penalty.
Danny Invincible replaced Ford at the interval as Killie boss Jim Jefferies went for a more attacking line-up.
Caley started the half strongly, with McGuire shooting wide from Grant Munro's centre.
Kilmarnock were clearly still seething from the penalty award and Frazer Wright was booked for a late tackle from behind on Imrie, while Vigurs was cautioned for a late tackle on the impressive Taouil.
Seconds after being booked, the young Caley midfielder found the side-netting with a fierce drive.
Hamill was booked for fouling Vigurs after 61 minutes as the game looked like turning nasty.
Jefferies was told to calm down by referee Brian Winter after sarcastically applauding when Kilmarnock were awarded a decision. Fernandez was then cautioned for a similar act of sarcasm.
Imrie was brought down by Pascali inches outside the box after 72 minutes but the midfielder's free-kick was blocked by Fowler.
Kilmarnock made a double substitution after 74 minutes with Gavin Skelton and Donovan Simmonds replacing Bryson and Sammon.
Inverness freshened things up themselves a couple of minutes later, with Don Cowie replacing McBain.
Kilmarnock's day got worse when they were reduced to 10 men, with Fowler given a second booking for handball.
Inverness looked to have sealed their victory when Black rose to head home an Vigurs corner and the best efforts of Fernandez could not stop the ball creeping under the bar.
Craig Brewster brought on Adam Rooney and Barry Wilson for Barrowman and Vigurs with the game drawing to a close.
Rooney could have added a fourth for Caley just before the end but the Irishman headed wide.