The Giallorossi, seeded for the first knockout round of the competition after topping Group E, will face the Spanish side, who finished second in their group.
The first leg, at El Madrigal, will take place on Thursday 16 February.
The return leg at the Stadio Olimpico is scheduled for the following week, Thursday 23 February.
The two sides have met previously in the competition, when it was known as the UEFA Cup: Villarreal winning 3-2 on aggregate in the fourth round back in 2003-04.
The Spanish side gained nine points from a group topped by Turkish side Osmanlispor, with Zurich and Steaua Bucharest the other participants.
El Submarino Amarillo ('The Yellow Submarine') reached the semi-finals of last season's competition, losing out to Liverpool. They reached the same stage in 2010-11, when they were eventually beaten by Porto.
Roma finished top of Group E after going unbeaten in their six games - with 12 points from meetings with Astra Giurgiu, Viktoria Plzen and Austria Wien.
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