Kensuke Nagai began the scoring in the first half before Maya Yoshida and Yuki Otsu added further gloss to the scoreline in the second period as Takashi Sekizuka's side capitalised on their man advantage following the 41st-minute sending-off of Saad Saadeldin.
The Samurai Blue progress to the last four and another knockout match on Tuesday at Wembley, while Egypt head home wondering what could have been after their last-gasp qualification from the group stage.
Fresh from topping Group D with two victories and a draw, Japan started the quarter-final brightly, Daisuke Suzuki having the first opportunity of the encounter but failing with a header from Takahiro Ohgihara's free-kick after ten minutes.
Four minutes later, Japan were in front. Hiroshi Kiyotake won possession in midfield and found Nagai, who took advantage of confusion between Egypt goalkeeper Ahmed Elshenawi and his defence to grab his second goal of the tournament and put the Asian side ahead.
The Nagoya Grampus striker was injured during the move, however, and had to be substituted shortly after, with Manabu Saito his replacement.
Egypt attempted to respond, with Mohamed Aboutrika sending a header well wide, Hiroki Sakai having to clear a dangerous cross from Ahmed Fathi, and Eslam Ramadan firing a free-kick over from a promising position.
The African side's growing pressure was deflated four minutes before half-time, though. A fast counter-attack by the Japanese concluded with Saad committing a professional foul on Saito. The referee produced a red card for the defender, leaving Egypt coach Hany Ramzy with a lot of work to do at the break.
A goal and a man up, Japan controlled the action in the second half, effectively restricting any attacks from the Egyptians, who could not find any way through a stubborn defence.
The match was ended as a contest in the 79th minute, when defender Yoshida connected with a Kiyotake set-piece to head past Egypt 'keeper Elshenawi.
And the icing was added to the cake four minutes later, courtesy of another cross. This time it was Ohgihara who delivered for Otsu to head into the net and make Japan the first team to reach the semi-finals at London 2012 where they will face the winners of the match between Mexico and Senegal.