Salah converted a 43rd-minute penalty amid an electric atmosphere at the Borg El Arab Stadium.
Egypt avenged a humiliating World Cup defeat by Ghana three years ago with a 2-0 victory Sunday in a 2018 African Group E qualifier before an 85,000 crowd in Alexandria.
Ghana triumphed 6-1 in the first leg of a 2014 World Cup play-off to set up an aggregate victory that prolonged the agony of Egypt, who have not competed at the finals since 1990.
Mohamed Salah converted a 43rd-minute penalty amid an electric atmosphere at the Borg El Arab Stadium and Abdallah Saied doubled the lead four minutes from time with a close-range shot.
Ghana, seeking to qualify for a fourth consecutive World Cup, dominated second-half possession without finding a way past 43-year-old goalkeeper Essam El Hadary.
El Hadary is the lone survivor of the national team of the previous decade that won three straight Africa Cup of Nations titles, but repeatedly failed to secure World Cup qualification.
Egypt have six points after two rounds, Uganda four, Ghana one and Congo Brazzaville are pointless.
The remaining four rounds are scheduled between August and November 2017 with the group winners qualifying for the 2018 World Cup in Russia.
Salah put Egypt ahead with a spot-kick that just avoided the legs of diving goalkeeper Razak Brimah after Harrison Afful fouled Mahmoud Hassan.
Emmanuel Agyemang-Badu came agonisingly close to equalising early in the second half with a glancing header that flew narrowly wide.
A late counterattack caught out Ghana and a couple of square passes set up Saied to turn and score with a low shot into the corner.
Farouk Miya scored after 18 minutes to give bottom seeds Uganda a 1-0 win over Congo in Kampala Saturday.
Democratic Republic of Congo regained first place in Group A on goal difference from Tunisia after a 2-1 comeback victory over Guinea in Conakry.
The match was won through two goals in quick succession during the second half from England-based attackers.
Neeskens Kebano from second-tier club Fulham equalised on 54 minutes and Everton flier Yannick Bolasie snatched the winner two minutes later.
Seydouba Soumah had raised Guinean hopes of a first group win by converting a 23rd-minute penalty.
DR Congo and Tunisia have six points each and Guinea and Libya are pointless in the only mini-league where two teams have won twice.
Egypt and Group B pacesetters Nigeria are the other countries boasting a maximum six points from two matchdays.