Hosts' boss Craig Brewster dropped Don Cowie in favour Iain Vigurs, while Killie were without defender Garry Hay, who is carrying a knee injury.
Inverness keeper Michael Fraser came back in for Ryan Esson, who played in the extra-time win against Morton in the Co-operative Insurance Cup.
It took only four minutes for the visitors to steal into the lead. Frazer Wright lofted in a free-kick and keeper Fraser failed to deal with it, Conor Sammon was on hand to knock the ball home from eight yards.
The Highlanders almost replied after 15 minutes when Andy Barrowman fed the ball to Roy McBain, but the midfielder shot well wide.
Moments later Sammon leapt to head a Barrowman effort off the line from a Vigurs corner.
The Inverness men were back level on 21 minutes when Phil McGuire shot home from the edge of the box after a Richard Hastings free-kick was not properly cleared.
Twice after that Ian Black was denied with fierce shots by keeper Alan Combe as Inverness upped the tempo.
Their chance to get in front arrived for Inverness just three minutes from the interval when Craig Bryson seemed to take down Barrowman.
After protests from Killie produced yellow cards for Combe and skipper James Fowler for dissent, the former Birmingham forward smashed the ball high into the net.
Killie's job in the second half would be getting a grip of the game again which the Caley Jags were now in control of.
Challenges were frequent and yellow cards were flashed for fouls by Vigurs and Jamie Hamill.
Chances were few and far between in the second period and Killie's task became harder when Fowler's second booking for deliberate handball forced him off the pitch.
The gloss was added to the result with ten minutes to go when the diminutive Ian Black headed home a corner from Vigurs, despite an attempt on the line to keep it out.