The Black Stars needed two wins in their last two qualifying games and are now left at bottom place in Group F.
Ghana have failed to reach the Africa Cup of Nations for the first time since 2004 after drawing with Angola 1-1 in their qualifying match.
The Black Stars needed a win in their penultimate group game on Friday to keep alive their slim hopes of qualifying for the 2025 tournament in Morocco.
Ghana, four-time Africa Cup champions, have played in 24 editions of the tournament. Only seven-time champions Egypt (26) and defending champions Ivory Coast (25) have appeared in more.
Angola, which had already qualified, made a better start in front of the home fans in Talatona. But Ghana veteran Jordan Ayew opened the scoring for the visitors with a brilliant free kick from distance in the 18th minute.
M’Bala Nzola had a chance to equalise with a penalty only for Ghana goalkeeper Abdul Manaf Nurudeen to save his spot kick.
The home team kept pushing, however, and Felicio Milson set up Zini to equalise in the 64th.
Ghana remained bottom of qualifying Group F with just three points from five games. They needed two wins from their final two games while hoping group rival Sudan (seven points) lost both of their games.
Niger had earlier done the Black Stars a favour by beating Sudan 4-0.
Ghana next play Niger (four points) on Monday. Niger can qualify as group runners-up behind Angola (13 points) as long as Angola beat Sudan in their final group game. Niger have a better goal difference than Sudan.
Former Hertha Berlin winger Myziane Maolida scored in the last minute for Comoros to qualify with a 2-1 win over The Gambia. It is just the second time the island nation team have qualified for the Africa Cup.
Zambia, Mali, and Zimbabwe also secured their qualification on Friday, while Nigeria, Tunisia, South Africa, Uganda, Equatorial Guinea and Gabon clinched their spots on Thursday.
Victor Osimhen’s late goal was enough for Nigeria to progress with a 1-1 draw against Benin.
Morocco, Burkina Faso, Egypt, Algeria, DR Congo , Cameroon, Senegal, Ivory Coast, Equatorial Guinea and Angola had already qualified before this round of games.
There are still five places available in the 24-team tournament with qualifying continuing through Tuesday.