In a rematch of the climax to last year's European season, the defending champions pulled ahead of their Russian opponents in the first quarter and never looked back, leading 40-28 at halftime.
The Moscow team staged a comeback in the second half, cutting the lead to single digits, but strong defending by Olympiakos forward Kyle Hines helped his team hold on for victory.
CSKA's Sonny Weems, formerly of the NBA's Toronto Raptors, and Olympiakos pair Pero Antic and Hines led the scorers with 13 points each.
The Greek team contained CSKA to 14 of 45 shots from the field and did a great job of neutralising their Serbian playmaker Milos Teodosic.
Having averaged 13 points and five assists up to the Final Four, he scored just five points and had only one assist.
Six-times winners CSKA were trying to avenge last year's defeat in the final in Istanbul where they blew a 19-point lead in the second half and lost to a game-winning shot at the buzzer by Georgios Printezis.
Friday's second contest will see Spanish giants Real Madrid take on arch rivals Barcelona for a berth in Sunday's championship match. (Reporting by Mike Szabo; editing by Patrick Graham and Tony Jimenez)