A hat-trick from Michael Higdon proved decisive as Motherwell left Caley Thistle still searching for their first SPL victory of the season.
There was one change to the Inverness side that had triumphed 2-0 at Arbroath in the second round of the Scottish Communities League Cup in midweek.
Captain Richie Foran returned from a two-game ban to take the place of Billy McKay, who dropped to the bench.
That was Caley Thistle's line-up pre-match, but an injury sustained by Simon King in the warm-up meant David Raven having to be promoted from the substitutes. His place was taken by on-loan Arsenal forward Philip Roberts.
The late change clearly disrupted Inverness, who found themselves 2-0 down with just 12 minutes gone.
Firstly, Tom Hateley's corner in the 10th minute curled in at the near post, despite Ryan Esson's best attempts, before Michael Higdon doubled their lead two minutes later, finishing from six yards following great play by Chris Humphrey.
Inverness slowly regained their composure and got themselves back into the contest with 28 minutes gone, Foran heading home from Owain Tudur Jones lofted pass.
Foran then had a chance to square matters before the interval, but was denied by Darren Randolph.
If the first half had been pulsating then the second period did not disappoint either.
Both teams had chances before Higdon seized upon a short back pass from Raven in the 72nd minute to restore Motherwell's two-goal lead.
Seven minutes later, Henrik Ojamaa surged down the right and crossed for Higdon to power an effort into the roof of the net and complete his hat-trick.
Caley Thistle did have an opportunity to reduce the leeway but Andrew Shinnie saw his spot-kick saved by Randolph after Foran had been felled by Jonathan Page.
MOTHERWELL - Randolph; Kerr, Francois Angol, Cummins, Page, Hateley, Humphrey (Carswell, 84), Lasley, Higdon, McHugh (Ojamaa, 72), Law (Murphy, 63). Subs unused: Daley, Murray, Hollis. Booked: Page.
CALEY THISTLE - Esson; Meekings, G. Shinnie, Warren, Raven, Tudur Jones (Morrison, 63), Sutherland (McKay, 79), Draper, Foran, A. Shinnie (Pepper, 81), Doran. Subs unused: Laing, Polworth, Roberts, Reguero. Booked: G. Shinnie.
Referee: S. O'Reilly.