Defending champs Pyramids meet FAR Rabat, while 12-time kings Al Ahly clash with Esperance.
In the final match-up of the last eight CAF Confederation Cup champions RS Berkane of Morocco will meet Al Hilal of Sudan.
Masandawana secured their spot in the quarterfinals with a 2-0 victory against Algeria’s MC Alger, coached by Rulani Mokwena, in the last group stage encounter.
Sundowns will play the first-leg against Stade Malien at home on 13-14 March before traveling to Mali on 20-21 March.
READ: Makhaula: ‘We’re Ready to End Sundowns’ Era’
CAF Champions League quarterfinal draw
RS Berkane (MOR) v Al Hilal (SUD)
Esperance (TUN) v Al Ahly (EGY)
Mamelodi Sundowns (RSA) v Stade Malien (MLI)
FAR Rabat (MOR) v Pyramids (EGY, holders)