Marco Asensio and Francisco "Isco" Alarcon were the big winners in a match that had little at stake for Real Madrid.
Asensio and Isco used to have bigger roles for Madrid but haven't been getting many first-team opportunities under new coach Santiago Solari.
"I'm very happy for Isco and I'm also very happy for Asensio and Vinicius," Solari said.
"They could all be starters for us, otherwise they wouldn't be here." Vinicius played well throughout and claimed his second goal for Madrid with a shot from inside the area in the 75th minute at Santiago Bernabeu Stadium.
Isco was a starter for the first time under Solari and was named captain. He hadn't scored a goal since September but one of his strikes against Melilla came from a superb long-range shot into the top corner.
Mariano Diaz went off near the end because of an apparent muscle injury, while Madrid youth players Fran Garcia and Alvaro Fidalgo came on for their debuts as second-half substitutes.
Eibar rallied from 2-0 down on Thursday but was eliminated 4-2 on aggregate.
Athletic Bilbao repeated the 4-0 result from the first leg against Huesca to advance 8-0 overall. It was the third win for Athletic in 16 matches this season, and the team's first match since Argentine coach Eduardo Berizzo was fired.
Real Betis defeated third division Racing Santander 4-0 to go through 5-0 on aggregate.
Barcelona, Atletico Madrid and Sevilla went through on Wednesday. The draw for the last 16 will be on Dec. 13.
(With inputs from agencies.)