John Sutton gave Motherwell an early lead but Anthony Stokes bundled home from close range in first-half stoppage-time before Paul Hanlon did the same despite suspicions of handball.
Liam Miller doubled the advantage for Hibs and unlike last season, when they lost a four-goal lead to draw 6-6, the visitors held on despite Jamie Murphy pulling one back from the spot.
Motherwell manager Craig Brown brought strikers Esteban Casagolda and Nick Blackman off the bench for their debuts but Hibs killed the game off to get their Scottish Premier League campaign off to a winning start.
The teams had experienced contrasting fortunes in the Europa League, with Motherwell setting up a play-off tie against Odense with victories over Breidablik and Aalesund while Hibs shipped six goals as they fell to Maribor.
Motherwell started brightly but almost fell behind in the fifth minute when Stokes took advantage of a slip by Mark Reynolds, but Darren Randolph steered the Irishman's effort wide with his foot.
The home side were soon back in the ascendancy with Murphy testing Graham Stack from outside the box.
Well took the lead in the 13th minute when Sutton got in front of Chris Hogg at the near post before getting a deft touch on Tom Hateley's low inswinging cross to guide the ball inside the far post.
Motherwell continued to look dangerous and Sutton had a shot saved before Sol Bamba denied with an excellent block following Murphy's low cross.
The game was being played at a furious pace and Motherwell were looking sharp. Hateley's curling effort was held by Stack and Bamba's long legs again denied Sutton as he attacked Steve Jennings' near-post cross following slick build-up play.
But Randolph again came to Motherwell's rescue when he pushed over Kevin McBride's powerful 16-yard strike following a poor clearance from Reynolds.
And Hibs levelled when Bamba headed down Derek Riordan's inswinging free-kick for Stokes to sweep home from two yards.
Motherwell came back out intent on restoring their lead and Stack held Murphy's low shot after Keith Lasley's long pass almost sent the Scotland Under-21 striker clean through, before Reynolds flashed a 30-yard strike just wide.
Randolph produced another great save when he pushed away a stunning 30-yard shot by Stokes from wide on the left.
The home side were still creating more chances than their visitors and Stack held Murphy's flick with the outside of his right boot after a ball over the top from Reynolds.
Motherwell went closer still when the improving Chris Humphrey beat Hanlon on the right wing and looped a cross off the inside of the post. The ball eventually came back to Humphrey, whose second cross was headed just wide by Sutton.
However, Hibs took the lead in the 64th minute after another brilliant delivery by Riordan. The former Celtic player swung the ball towards the back post and Hanlon forced it over the line, although the ball appeared to come off his arm.
Sutton had a strong penalty claim dismissed by Craig Thomson after he was clumsily bundled over by Hogg, and Hibs immediately went further ahead in the 73rd minute when Riordan played Miller into the left channel for the Irishman to drill home.
Blackman came on, with Hateley making way, and the on-loan Blackburn striker quickly won a penalty when Colin Nish senselessly pulled his shirt amid little danger just inside the box.
Murphy sent Stack the wrong way to make it 3-2 with 15 minutes remaining.
But the comeback never materialised this time as Hibs took the sting out of the game.
Brown brought on Spaniard Casagolda to play with four strikers but Hibs looked dangerous on the break and both Riordan and Stokes went close before Hibs substitute David Stephens ensured victory by blocking Lasley's last-gasp shot.