But Erik ten Hag rang the changes for the second half and Rashford helped himself to a double either side of a Martial strike to give the Red Devils all three points, with Nikolas Panagiotou scoring a late consolation.
LiveScore reports that United have now won six of their last seven Europa League away games and remain second in Group E, three points behind leaders Real Sociedad.
Tyrell Malacia was caught in possession and the hosts steamed forward on the break. Bruno perfectly played in Ansarifard, who fired past David de Gea.
Rashford was introduced at half-time and levelled for United within eight minutes of coming on, latching onto a sublime Fernandes diagonal before cutting onto his right foot and smashing home.
Martial put the visitors in front just a minute after making his way onto the pitch, as a clever Rashford flick teed him up to lash into the bottom corner.
Ronaldo hit the woodwork late on, but provided an assist as his cross-shot picked out Rashford at the back post to tap in for his second.
Omonia grabbed a goal back through Panagiotou, but United saw the game out to earn an important victory, LiveScore reported.
Contact: theeditor[at]punchng.com