Motherwell substitute Lionel Ainsworth netted a late winner as Caley Thistle suffered a first defeat in 2015.
Louis Laing headed the Steelmen in front three minutes after the restart before Caley Thistle’s new signing Edward Ofere restored parity.
But a deflected drive from Ainsworth six minutes from time claimed victory for Motherwell, who ended the match with ten men after Simon Ramsden’s red card.
Ofere, who joined the Caley Jags on Friday, was handed his Caley Thistle debut after receiving international clearance in time for the match.
Daniel Devine was drafted into the starting line-up with Marley Watkins and Gary Warren both missing out due to suspension.
Motherwell had also bolstered their attack this week by bringing Aussie Scott McDonald back to the club.
The 31-year-old former Celtic, Middlesbrough and Millwall forward, led the line for the Steelmen as they looked to end an eight game winless run.
The hosts made a promising start to the match with McDonald heading over in the opening minutes before firing over from close range after Josh Meekings failed to deal with Stephen McManus’ long, hopeful pass forward.
Greg Tansey went close with a viciously-struck long range effort before a Danny Williams drive was deflected over as Caley Thistle tried to muster a response to the early Well pressure.
Ofere was given a bruising introduction to Scottish football just after the hour mark when Simon Ramsden received a yellow card for a wild challenge on the Nigerian.
The visitors should have taken the lead just before the break when Danny Williams pounced on Josh Law’s weak header but the Englishman was unable to round Well stopper George Long.
And Caley Thistle were made to pay three minutes after the restart when Laing headed home Conor Grant’s perfect cross to the delight of the home support.
The Inverness men almost made an immediate response with Williams unfortunate to see his fine effort from 25 yards strike the cross bar with Long well beaten.
Caley Jags went even closer after 54 minutes when Nick Ross floated a cross to the back post for Ofere whose downward header struck the inside of the post before being cleared to safety by Stephen McManus.
A change was needed for Inverness and John Hughes opted for an extra forward, brinigng on Calum Ferguson for Williams.
The visitors began to dominate and the equaliser arrived with 14 minutes to go when Ofere headed home a Graeme Shinnie cross.
But there was still life left in Motherwell and the Fir Park side netted the winner with six minutes left when substitute Ainsworth’s shot deflected into the net off Draper.
Motherwell ended the match with 10 men when Ramsden was sent off for a second bookable offence for a poorly timed challenge on Ryan Christie