Leigh duo Peter Mata'utia and Matty Dawson were sent off as Leeds rammed home their Super League quality to win 52-22 and march into the Ladbrokes Challenge Cup semi-finals.
Centurions full-back Mata'utia made a dangerous lift on Rhinos hooker Matt Parcell in the 10th minute and was given his marching orders by referee Chris Kendall before winger Dawson followed suit for dissent in the closing stages.
Leigh had struck first through prop Nathan Mason's close-range score but Brian McDermott's side took control after Mata'utia's sending off and led 40-12 at the break.
Leeds Rhinos' Jordan Lilley is tackled by Kevin Larroyer of Leigh Centurians
They ran in a total of seven first-half tries to seal their place at the Macron Stadium in Bolton for the Challenge Cup semi-finals on August 5 as part of a historic double-header.
Leeds had beaten Leigh at this stage of the competition in 2012 and 2014 but this latest meeting was switched to the home of Featherstone Rovers because of the Test match cricket taking place at Headingley.
McDermott was left with three injury concerns as Parcell was forced off midway through the first half with concussion while Carl Ablett and Jimmy Keinhorst also departed during the opening period.
After Mason's opener and Mata'utia's red card, Leeds took the lead when winger Tom Briscoe scored in the 11th and 17th minutes.
The Rhinos began to motor and homegrown full-back Jack Walker