First-half goals from Lionel Ainsworth and John Sutton allowed Stuart McCall's men to draw level on points with Aberdeen, albeit they have played a game more.
However, the result meant further heartache for Inverness just three days after losing the League Cup final on penalties to the Dons.
Despite such a physically and emotionally draining experience at the weekend, boss John Hughes opted to make just one change for the visit to Fir Park.
Aaron Doran was added to the side, while Marley Watkins dropped to the bench and Gary Warren was also named among the substitutes after returning from suspension.
Gunnar Nielsen started in goal for the Steelmen, with regular first choice goalkeeper Lee Hollis out of action for around a month with a broken finger, and Stevie Hammell and Stuart Carswell were also added to the starting line-up.
Motherwell fired out an early warning when Hammell flashed a dangerous ball across the face of goal for Sutton but he was unable to connect and stab home from close range with just six minutes on the clock.
Inverness shrugged off the early scare and quickly set about putting their hosts under pressure when Billy McKay collected James Vincent's knockdown and stung the palms of Nielsen with a point-blank shot.
McKay was threatening again moments later, David Raven the provider this time with a cross into the box, but again the goalkeeper came to the rescue with a decent block.
At the other end, Dean Brill was called into action to prevent a well-struck effort from Ainsworth from finding the back of the net - but he could not deny the Motherwell man the opener on 25 minutes.
A great ball from Hammell teed up Ainsworth, who dispatched a right-footed shot into the bottom corner to put the home side in control of the match.
Motherwell were cruising nine minutes later when they doubled their lead. Hammell was the provider again, delivering into the path of Sutton, who sent a stooped header beyond Brill from a few yards out.
Inverness made a change at the interval, swapping Doran for Ryan Christie, but Well almost had the net bulging again shortly after the restart.
James McFadden was not too far away with a volley that dipped just over the crossbar four minutes into the second half.
The Highlanders were desperate to haul themselves back into the game and Nielsen saved well from Vincent, before a powerful rebound effort from Richie Foran was cleared off the line by Shaun Hutchinson.
Christie then dragged his shot inches wide of target from 20 yards but Inverness could find no way back and Motherwell held on for the win.