Three goals in seven minutes destroyed Hibs' unbeaten record and gave Motherwell a thoroughly deserved victory.
Hibs tried to come back in the second half but Motherwell were well organised at the back and broke with menace when they had possession.
Clayton Donaldson returned to the Hibs line-up after suspension and he took just 11 minutes to make his mark.
He skinned Paul Quinn and Keith Lasley on the halfway line before homing in on goal and tucking the ball past Graeme Smith.
It was just the start that Hibs wanted and Smith had to be on his guard moments later to clutch a mishit cross from Lewis Stevenson which almost crept in under his crossbar.
David Murphy, playing in a more advanced midfield role, then curled a 25-yard free-kick well over the top.
But Motherwell were level after 17 minutes when David Clarkson beat Yves Makalamby with a near-post header from a Ross McCormack corner.
Three minutes later, Motherwell were in front when Keith Lasley was unmarked at the back post and he volleyed home after a great cross from Steve McGarry.
Worse was to follow for Hibs as McCormack made it 3-1 after 24 minutes when McCormack spied Makalamby loitering off his line and chipped the ball over him from 30 yards.
Hibs were clearly shell-shocked and Clarkson almost made it four when he was given too much time in the box but Makalamby saved with his legs.
Hibs changed it at half-time and sent on Merouane Zemmama and Filipe Morais is a bid to turn the tie around.
Smith pulled off a wonderful save to keep out a header from Rob Jones after 49 minutes and Morais sent a couple of efforts high and wide.
Zemmama was just a foot away with a 20-yard shot which caught Smith flat-footed and then the goalkeeper did well to save at the feet of Donaldson.
But it was by no means backs-to-the-wall stuff and McCormack curled in a 25-yard free-kick which was slapped away by Makalamby.
Guillaume Beuzelin brushed the side-netting at the other end with a 20-yard shot after good work by Mickael Antoine-Curier.
But Chris Porter killed the tie seven minutes from time when he shot home after McCormack had set him up.
Antoine-Curier scored a late consolation for Hibs but by then the tie was dead.