Dylan Hartley was sent off on his 50th European Cup appearance for Saints as they saw their hopes of glory fade at Franklin’s Gardens.
Hartley had only been on the field for six minutes when he was shown a red card by referee Jerome Garces.
The hooker swung his arm into the face of Leinster flanker Sean O’Brien, who was forced off injured.
And though Saints battled with 14 men, they were eventually thrashed 37-10, having conceded five tries.
Jim Mallinder’s men were 20-10 down when Hartley’s red mist moment occurred, with Garry Ringrose and O’Brien having scored for Leinster.
Ahsee Tuala, a 25th-minute replacement for Jamie Elliott, had given Saints hope with a well-worked try, but Leinster got their control back and cruised after Hartley’s departure.
Saints had spoken in the build-up about the need to start fast, but they were to concede inside just two minutes as Ireland centre Ringrose finished off a move under the posts after great work from full-back Rob Kearney.
Nacewa converted with ease to give the away side a 7-0 lead and it was all Leinster, with their travelling army of supporters in high spirits.
They soon had even more to shout about as their side smashed Saints at the scrum, winning a penalty that Nacewa kicked to take his team into double figures.
It was all Leinster, who had been 26-0 up in their visit to the Gardens on the same weekend three years earlier, and they were threatening to run riot.
Saints needed to stem the tide, they needed a catalyst, and skipper Tom Wood put in a captain’s hit to fire his team up.
Mallinder’s men pushed up the pitch and earned a penalty, which Myler slotted to get his team’s first points on the board.
Suddenly Saints were up and at them, putting the squeeze on Leinster and they came close to scoring, with Jamie Elliott just not able to gather in the corner at the last.
Elliott was forced off injured after taking the hit, bringing Tuala into the action from the bench.
Tuala soon lined up Nacewa with a jackhammer hit that added more fuel to the Saints fire and the home side were now playing with real intensity.
There were echoes of the Dublin defiance of three years ago as Saints held out on their own line before the break,
Sean O’Brien thought he had punctured the home side, but his try was ruled out as the flanlker was deemed to have knocked on in the build-up.
And Saints made the most of their reprieve just after the break as a brilliant break and eventually a fine pass from JJ Hanrahan set up Tuala in the corner.
Myler converted brilliantly from out wide and suddenly the scores were level, with Saints tails up.
But Nacewa responded with a long-range penalty and Leinster were soon crashing their way over the line, with their forwards packing a punch to help O’Brien score.
Nacewa converted to take his team 10 points up with 23 minutes to go, and Saints again had a mountain to scale.
And it soon became mission impossible as Hartley was sent off for a dangerous tackle on O’Brien.
Saints battled bravely, but they were undone again when a fine crossfield kick from Ross Byrne was gathered by Rory O’Loughlin, who dived over the line.
Nacewa missed the conversion, but the game was over as a contest, with only Leinster’s search for a try bonus point causing any intrigue.
And the Irish side were to get it as Jamison Gibson-Park weaved his way inside some slack Saints defending to score his team’s fourth try.
Nacewa converted as a sea of dismayed fans flooded out of Franklin’s Gardens while the on-field agony continued for the final few minutes.
There was still time for George Pisi to be sin-binned and Nacewa to score Leinster’s fifth to leave the blue flags flying at the Gardens as Saints slumped to the turf.
Saints: Foden; K Pisi, Burrell, Hanrahan (G Pisi 65), Elliott (Tuala 25); Myler, Groom (Kessell 70); A Waller (E Waller 62), Haywood (Hartley 52), Hill (Denman 66); Paterson (Ratuniyarawa 57), Lawes; Gibson, Wood (c) (Haywood 60), Picamoles (Harrison 57).
Leinster: R Kearney (O’Loughlin 43); A Byrne, Ringrose, Henshaw, Nacewa (c); Carbery (R Byrne 16), L McGrath; J McGrath (Healy 59), Cronin (Tracy 59), Furlong (Bent 65); Toner, Triggs (Ruddock 52); O’Brien (Conan 58), van der Flier, Heaslip.
Referee: Jerome Garces (France)