The Northern Irish keeper produced a superb save from Marco Schneuwly's spot-kick, the second of the Swiss side's five, and extra-time substitute Tam Scobbie completed a perfect set for Saints to give the Perth men a 5-4 triumph.
A mini pitch invasion at the climax, which could get the club into trouble with UEFA, was the only negative on another historic night for the Scottish Cup winners.
Following a 1-1 draw in Lucerne last week, the sides battled to the same scoreline over 90 minutes in the return leg at McDiarmid Park.
A 23rd-minute penalty from fans' favourite Stevie May gave St Johnstone a one-goal advantage, with the comfort of an away goal also in the bag, but Schneuwly, just four minutes after being introduced in the 54th minute from his surprise place on the bench, ensured the teams finished regulation time all square.
Saints substitute Liam Caddis crashed a shot off the upright just two minutes from the end of extra time and it was left to penalties to separate the teams after three and a half hours of football.
Steven MacLean, Caddis, Dave Mackay - who missed in last year's agonising penalty-kicks defeat to FC Minsk - and May left it on the shoulders of Scobbie, who made no mistake with an emphatic fifth.
The Perth men recalled May after a thigh injury and Michael O'Halloran also started, with Liam Caddis and Lee Croft dropping to the bench.
Saints had to weather something of an early storm as the Swiss outfit sought the goal that would put them ahead in the tie.
There were only two minutes on the clock when the recalled Oliver Bozanic curled an effort over the bar as the visitors signalled their intent.
May put early pressure on the Swiss defence as he chased a long ball that brought keeper David Zibung racing off his line to head clear. The ball fell kindly 40 yards from goal for MacLean but the striker could not gain control quickly enough and his eventual attempt was blocked.
Luzern came close to the opener as the diminutive Jamir Hyka curled a beautiful cross to the back post but Adrian Winter volleyed across goal. Winter's free-kick then somehow evaded his diving team-mates.
However, having emerged unscathed and seen Bozanic substituted with a back injury, the McDiarmid Park side took the lead midway through the half.
David Wotherspoon's corner troubled the visitors and Belgian referee Jonathan Lardot adjudged Hochstrasser to have hauled down Gary Miller.
May, scorer of 27 goals last season, blasted the spot-kick into the top corner as Zibung dived the wrong way.
Luzern responded and Chris Millar made a heroic block before Remo Freueler brought a magnificent diving save from Mannus. With the ball falling to the visitors six yards out, Saints were relieved to see Dario Lezcano miskick wide.
Five minutes from the interval, St Johnstone broke Luzern's growing stranglehold and Millar strode forward but his stinging drive from 25 yards arrowed just wide.
Luzern appealed strongly for a penalty of their own in the 50th minute as Lezcano threw himself theatrically down, but Lardot waved play on.
Again Saints showed resolve and broke with ambition when they could, but the sight of Schneuwly, the scorer of the equaliser last week, springing from the bench after 54 minutes would not have eased the home side's concerns.
And within four minutes the substitute had the tie back all square with a horrible goal as far as Saints were concerned.
A short corner gave Hyka space to fire a cross into a congested box. The home side could not get a decisive boot on the bobbling ball and it fell kindly for Schneuwly to poke home through a forest of legs.
Schneuwly blasted just wide two minutes later whilst Mannus had to palm away another blistering drive from Winter.
Mannus carefully dealt with Schneuwly's shot on the turn and the Swiss looked the more likely as time wore on.
May, who had been kept quiet since the break, lifted a shot just over three minutes from time as both teams sought a winner in vain.
Four minutes into the first period of extra time, Wotherspoon engineered some space for himself but his left-foot curler drifted just beyond the far post.
Two efforts from Winter could not find the target and early in the second period of extra time Lezcano screwed his shot wide when it appeared easier to score from 12 yards.
May fluffed one shot after a barnstorming run in from the left flank but, when substitute Caddis struck the post with a snap effort from Lee Croft's low cross, the inevitability of penalties followed moments later.