Mata clipped home from Henrikh Mkhitaryan's low cross to send the Reds into the last eight - but we were indebted to stand-in stopper Sergio Romero.
The Argentina pulled off four stunning saves as Rostov came to life after the break, including one of the season's best from Christian Noboa at the death.
The Reds lost Paul Pogba to a hamstring injury early in the second half and the world's most expensive player now faces an enforced absence.
United were completely dominant in the first half but struggled to find a way beyond Rostov's massed defensive ranks.
Nikita Medvedev saved well from an early Marcos Rojo header and Zlatan Ibrahimovic - available in Europe despite a domestic ban - struck the post from a tight angle.
United's positive attacking intent pinned Rostov back and we twice went close again in quick succession, with the Swede at the heart of everything.
He had a free-kick blocked by Andrei Prepelita and was then denied by Medvedev after Mata had delightfully played him through.
Despite the visitors need for an away goal of their own, the Russian side were intent to simply sit back and frustrate United.
Mkhitaryan had a penalty appeal waved away after he was shoved in the back but the elusive breakthrough then almost arrived on two occasions.
The Armenian's clever lob drifted inches wide and then Ibrahimovic unleashed an unstoppable effort that thumped back off the post for a second time.
Much-criticised Paul Pogba forced a good save from Medvedev on the stroke of half-time with the tie still in the balance but United ahead with the away goal.
With that in mind, the Russians came out of their shell and almost took a shock lead on 55 minutes.
Sardar Azmoun's 20-yarder was beaten out by Romero, and the keeper then saved well again from Miha Mevlja.
Ibrahimovic headed over the bar from Antonio Valencia's cross, but the Reds patience finally reaped the rewards with 20 minutes to play.
Mata scored from close range after neat link-up between Ibrahimovic and Mkhitaryan to take him into double figures for the season.
The closing stages became increasingly nervy with United reliant on Romero as a brilliant reflex stop thwarted first leg goalscorer Aleksandr Bukharov.
An even better save followed as the Argentine tipped over Noboa's free-kick from distance in the final action.
Overall team performance: 6/10
United Faithful Man of the Match: Sergio Romero
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