Two victories by the Cypriot club in Group K have come on the road, and this one happened after a collapse by Rostov over the final 10 minutes when they managed to score just 13 points.
A Fred House dunk with 1:50 to go in the third gave Rostov a 54-53 lead but the wheels came off soon after.
Quincy Taylor, who poured in 25 points, made one of his five three-pointers and Darrel Mitchell sank another right before the end of the third quarter for a 63-56 Proteas advantage.
Mitchell began the fourth with another three to open up a 10-point gap.
After Goran Nikolic made two free throws midway through the final quarter, Proteas were in complete command at 73-56.
Lokomotiv didn't score their first basket in the final period until Andrey Babichev connected from long range with 4:46 to go.
They weren't able to mount a serious comeback the rest of the way.
Vujadin Subotic had 21 points for Proteas, who host Cajasol Sevilla in their next game on February 24.
Dragan Raca's team was on target shooting the ball most of the night, hitting a very impressive 12 of 25 from long range and 17 of 28 inside the arc.
Taylor excelled with his three-point shooting, drilling five of seven.
House's 15 points topped the scoring for Rostov.
Daniel Yusup, coach of BC Lokomotiv-Rostov:
"Today we saw how one player can make [or break] a game. We played very well in the first quarter, when Antik was on the court. Then he was injured and my team stopped to play basketball."
"This was my first game in EuroChallenge for Lokomotiv-Rostov. I see that it's a team with great potential but we couldn't offer good basketball today."
Dragan Raca, coach of Proteas EKA AEL:
"Today my team played good basketball. We plan to capture first place in the group to have the most comfortable position in the next round."
"This is a very important win in this round."