Egypt had a mountain to climb after they were thrashed 6-1 by Ghana in the first game in Kumasi last month, and although they dominated and made two breakthroughs thanks to Amr Zaki and Mohamed Gedo, it was not enough to change their fortunes.
Finding at least five goals at home while keeping a clean sheet was always going to be a tall order, but with nothing to lose, the Pharaohs started off with intent against a Black Stars side who were surprisingly subdued before substitute Kevin-Prince Boateng scored in the 89th minute.
Mohamed Abou-Treika's long-range free-kick went close early on as it narrowly missed the Ghana net while Mahmoud Kahraba just failed to get on the end of a through pass as visiting goalkeeper Fatau Dauda cleared the danger.
However, Egypt did go ahead in the 25th minute when Dauda flapped at a free-kick fired in by Mohamed Aboutriaka, with Zaki on hand to steer the ball into the net.
Zaki went close again with a dipping strike in the 35th minute which Dauda tipped over the bar as Egypt threw everything at their opponents.
Ghana were under the cosh approaching half-time but Mohamed Salah's shot was saved by the keeper in stoppage time as the Black Stars went into the break looking fragile.
Egypt continued in the same vein at the start of the second half, with Gedo's shot on the turn blocked by the Ghana defence before Salah sent a curling effort over the bar.
Aboutriaka went close with a 57th-minute volley but time was beginning to run out for the Egyptians with four more goals needed to claim a stunning turnaround.
The hosts continued to push forward though and Salah saw a shot cleared off the line with just over 15 minutes remaining, before Michael Essien hacked the ball to safety for Ghana.
However they did find another score through Hull's on-loan striker Gedo, who slid the ball past a Dauda in the 84th minute.
Egypt could not make any more inroads though and Boateng pulled one back for the Black Stars late on with a simple finish from close range.
That was not enough to save Ghana from defeat on the day, but they had already done the hard work in the first leg as they sealed a third successive appearance in the World Cup finals.