A judge sentenced 34-year-old Jahlil Porter to at least 50 years in prison and 35-year-old Keith Garner to at least 40 years.
Authorities said two stepbrothers, 31-year-old William Taylor and 28-year-old Akeem Mattox, found some drugs while renovating a home.
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The brothers attempted to sell the drugs in November of 2018 which ultimately led to their deaths and those of two sisters, 20-year-old Tiyaniah Hopkins and 17-year-old Yaleah Hall, said police.
Prosecutors had sought 80-year prison terms, but the judge said the defendants should have the opportunity to appear before a parole board decades from now.
A third man was sentenced earlier to at least 25 years in prison but is seeking reconsideration of that term.
-- The Associated Press contributed to this report.