After a 1-0 victory in the quarter-final first leg in France last week, the Turin giants secured a 3-1 aggregate victory to progress to the last four of a European competition for the first time since the 2002-03 campaign.
Inspirational midfielder Andrea Pirlo struck the opening goal after four minutes with an exquisite free-kick from just outside the penalty area, but the visitors levelled when Jimmy Briand placed a header beyond Gianluigi Buffon 14 minutes later.
The Italian champions were not to be denied, though, and sealed victory on the night thanks to a long-range Claudio Marchisio strike that took a wicked deflection off Samuel Umtiti and gave goalkeeper Anthony Lopes no chance.
The victory extends Juve's unbeaten home record to over a calendar year, with their last defeat at the Juventus Stadium against Bayern Munich in the UEFA Champions League last April.
Leading scorer Carlos Tevez, who has been nursing a thigh injury but was passed fit, missed a third-minute effort as Antonio Conte's side wasted no time in stamping their authority on the game.
Then just a minute later Corentin Tolisso ended a typical bustling run from the Argentina striker on the edge of the penalty area and the midfielder was punished when Pirlo fired a trademark free-kick into the back of the net.
Juve's lead only lasted quarter of an hour, though, as Briand caught them out when he levelled with a close-range header.
From a quickly taken corner Arnold Mvuemba lifted a high ball to the back post, where Briand shrugged off a challenge from Marchisio and placed his header out of Buffon's reach.
Lyon were slowly getting into their stride and created the next opening just before the half-hour mark, with Maxime Gonalons meeting a cross on the edge of the area but Buffon parried his low strike away to safety.
A lacklustre start to the second half saw the hosts control possession without threatening the Lyon goal, in fact they had to wait until just after the hour-mark to test Lopes again.
The evergreen Pirlo whipped a cross into the penalty area for Tevez, who flicked a header into the top corner but saw his effort ruled out for offside.
Mvuemba tested Buffon with a free-kick in the 67th minute, but Lyon otherwise struggled to fashion goalscoring opportunities in the second half and a minute later they fell further behind in the tie.
Marchisio was given far too much room 25 yards from goal by the Lyon defence, and he made them pay by unleashing a strike towards goal that Lopes looked to have covered until the ball struck Umtiti and flew in the opposite direction and into the net.
Substitute Sebastian Giovinco wasted an opportunity to extend the hosts' lead further, but that never looked like being costly.
Conte's men now progress to the semi-finals and continue to dream of reaching the final, which will be held in their own stadium next month.
