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 leveled 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.
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Photo Credit: Getty