Former South Africa forward Motupa netted the first four goals as Wits crushed UD Songo of Mozambique 6-0 in Johannesburg after taking a 2-1 lead into the second leg.
Zimbabwean Terrence Dzvukamanja also scored as Wits achieved the biggest winning margin of the 15 ties with another to be completed Tuesday ahead of a November 10 group draw in Cairo.
It was the first time in seven attempts that Wits have qualified for the mini-league phase of a competition modelled on the UEFA Europa League.
Enyimba had a comfortable passage and Enugu a nervous one as both continued campaigns to become the first Nigerian winners of the Confederation Cup.
Having built a 2-0 advantage at home to South African second division side TS Galaxy, Enyimba doubled their aggregate advantage through goals from Daniel Darkwah and Martins Usule.
Galaxy finished 2-1 second leg losers in northeastern city Nelspruit when Terrence Mashego grabbed a consolation goal one minute from time.
– Most successful Nigerian club –
Enyimba are the most successful Nigerian club in CAF competitions, winning the Champions League and Super Cup twice in a row between 2003 and 2005.
None of the current Enugu team were born when the club won their only CAF silverware, the now defunct African Cup Winners Cup 42 years ago.
Rangers scraped into the group stage on away goals after edging Togolese visitors ASC Kara 1-0 through a Chinonso Eziekwe goal on 17 minutes that tied the aggregate score at 2-2.
Enugu also battled to overcome Pelican of Gabon in the previous round and need to improve if they hope to succeed Zamalek of Egypt as Confederation Cup trophy-holders.
Twice African champions Asante Kotoko, the lone Ghana challengers, bowed out after losing 2-0 in Abidjan to San Pedro of the Ivory Coast, who trailed 1-0 from the first leg.
San Pedro made the perfect start with Cheick Soumare scoring in the first minute and Tidjae Diomande netted four minutes from time to win the west African showdown.
Ghana, who rank among the African football powerhouses, have not won a CAF club competition since Hearts of Oak lifted the Super Cup 18 years ago.
There will be seven clubs from the west of Africa, six from the north, two from the south and one from the centre in the group draw, but none from the east
All seven clubs from the east, the weakest football region in the continent, were eliminated with the failure of Ugandan outfit Proline the biggest shock.
Holding Al Nasr of Libya 2-2 away seemingly set up the CAF debutants for an overall win, but they flopped in Kampala and lost 2-0 with Khalid Almaryami and Albedwi Osama scoring.
