Leicester boss Pat Howard's decision to hand youth its chance at Franklin's Gardens backfired as an under-strength Tigers outfit were mauled by Northampton.
England Under-19 internationals Tom Youngs and Ollie Dodge were handed their first starts for Leicester, but a Saints team, missing the likes of Carlos Spencer and Ben Cohen, scored two early tries to all but decide the derby before the break.
The experience of Northampton showed straight from kick-off as they broke the Tigers defence with ease.
Quick ball out to the right touchline allowed France Under-21 winger Matthieu Bourret, on his home debut, to run in the opening points of the EDF Energy group match and his first of the season.
Former rugby league star Stephen Myler was unable to convert, but he made no mistake from a penalty minutes later.
Northampton demonstrated their confidence as they chose the corner instead of the three points with their next penalty after yet more Leicester indiscipline.
The decision paid off for stand-in skipper Matt Lord as a rolling maul from the line-out allowed flanker Sam Harding to touch down, with Myler missing the subsequent conversion.
Howard's frustration intensified in the closing minutes of the half, with fly-half Ian Humphreys, who played so impressively for the Tigers in recent weeks against both London Irish and Wasps, missing two kickable penalties.
The chances of a Leicester comeback appeared to be extinguished five minutes into the second half as Humphreys pulled yet another penalty wide.
The home side continued to dominate as their back line and forwards worked magnificently to keep heavy pressure on the Leicester defence, with Kiwi Robbie Kydd commanding midfield.
Myler then stepped up to take a relatively simple penalty, but like his opposite number fluffed his lines and failed to add to Northampton's commanding lead.
Moments later a cross-field kick was athletically kept in play by Paul Diggin, who pushed the ball into the path of substitute Chris Wyles, allowing him to score his first try of the season. Myles missed the conversion.
The Tigers got their rolling maul in order in the final 20 minutes of the match as they pushed up the pitch, with flanker Luke Abraham scoring a deserved Leicester try.
But the shattered confidence of Humphreys was clear as he missed yet another kick at goal.
Leicester's pain continued late on as a kick for the corner from a penalty was completely misjudged by outside centre Matt Cornwell, resulting in a scrum for the Saints.
The Tigers capitulated in the final minutes, with errors creeping into their play, but despite the uncharacteristic Leicester loss Howard's men progressed into the semi-finals.