AshantiGold triumphed 2-1 at home against Etoile Sahel of Tunisia in western town Obuasi, but it was not enough as they suffering a three-goal hiding in the first leg of a second round tie two weeks ago.
Wits made a much meeker exit from the second-tier African club competition, losing 2-0 to modest AS Adema of Madagascar in Antananarivo after sharing two goals in Johannesburg.
Lamjed Chehoudi put the tie beyond the reach of AshantiGold by opening the scoring on 60 minutes before Theophilus Anubaah responded with two goals inside eight minutes to restore some Ghanaian pride.
The South Africans paid the price for fielding a reserve team in the first leg and boasts from a club official that they would atone on the huge Indian Ocean island proved hollow.
Aduana Stars of Ghana were ousted in the first round of the African Champions League by Wydad Casablanca of Morocco while SuperSport United of South Africa bowed out in the second round to Al-Ahly of Egypt.
Each country was permitted two entries on merit in each competition when the format was changed seven years ago, but consistently poor results have seen both surrender one place.
South Africa boasts the richest, best run league on the continent and Ghana is among the elite, yet weaker football neighbours like Zimbabwe and Mali had two clubs each in the 2011 Champions League and Confederation Cup.
Moghreb Fes, one of three Moroccan contenders for the title, appeared in trouble after being held 0-0 at home by Sahel, hoping to emulate compatriots ASFAN and become the second Nigerien club in a row to reach the group phase.
But Kader Fall gave the visitors a 10th-minute lead and although the Niamey outfit levelled early in the second half, Mohamed Chihani struck a late winner for a 2-1 victory on the day and on aggregate.
Another team to succeed on the road were African rookies Sunshine Stars of Nigeria as Dele Olundare snatched the only goal in Atlantic city Douala three minutes from full-time to complete a double over Tiko United from Cameroon.
Daring Club Motema Pembe of the Democratic Republic of Congo left it even later to snatch a 1-0 win over Victors of Uganda in Kinshasa with Nkanu Mbiyavanga scoring in the final minute after a drawn first leg.