Caley Thistle welcomed back captain Darren Dods to the centre of defence, with Stuart McCaffrey pushed out wide in place of Ross Tokely. Markus Paatelainen moved into a reshuffled midfield to accommodate Barry Wilson's absence.
Motherwell welcomed back Scott McDonald following his Celtic sabbatical. Jim Paterson returned to the midfield in place of Steven McGarry who was relegated to the bench.
Caley Thistle were a goal to the good after just 14 minutes. Russell Duncan's 20-yard deflected shot beat Graeme Smith, although Craig Dargo was credited with the final touch.
However, the warning signs were there - as less than a minute beforehand, Dods was on the end of Grant Munro's long throw from the left, and it broke to Paatelainen for a shot on target.
Motherwell were forced into an early change as McGarry came on for Kevin McBride who suffered an ankle knock.
McGarry quickly found his feet and only Dods' intervention prevented the former Ross County man nodding in Paterson's cross from the left on the half-hour.
On 40 minutes a lovely four-man move from Inverness down the left saw Richard Hart pass up a gilt-edged chance, but with the goal at his mercy he fired over.
Motherwell may have been happy to fight back from a 1-0 deficit after the break but, right on half-time, Caley Thistle put a different slant on Maurice Malpas' team-talk by doubling their lead.
Paterson conceded a free-kick in the Inverness half, the ball was pumped 50 yards high into the box towards the head of Graham Bayne. His knock-down found strike partner Dargo and he fired in from five yards out for his and Caley Thistle's second.
The need for change was evident from Motherwell's first-half performance and Paul Quinn came on for Danny Murphy at the re-start, but the visitors were still sloppy - Bayne almost pouncing on a Martyn Corrigan error, and Paatelainen then sniffing for a third as Brian Kerr nodded the ball back towards goal.
On 75 minutes Paterson crossed from the left for Krisztian Vadocz to hook in a rare Motherwell shot, but the effort lacked bite.
With five minutes left Paatelainen tried to flick a header across goal, Dods found himself facing the wrong way, but nodded out to John Rankin to fire a 20-yard arcing volley just wide of goal.