Viduka on the double for Boro
Aiyegbeni Yakubu's seventh goal of the season and a second-half double from Mark Viduka sent Boro to the top of Group D and left them needing just a point from their two remaining games to ensure their progression for the second successive season.
The Teessiders eventually won at a canter, although they did not have things all their own way until Yakubu broke the deadlock nine minutes before half-time in front of a crowd of just 12,953.
However, they ripped the visitors apart in 11 devastating second-half minutes to clinch their third victory in a week and all but ensure their place in the latter stages of the competition.
However, for 35 minutes or so, there was little to choose between the sides as Dnipro gave as good as they got.
Steve McClaren's much-vaunted 3-5-2 system, which paid such handsome dividends at the weekend against Manchester United, was nowhere near as effective against the slick-passing visitors.
After weathering the early exchanges, during which Gaizka Mendieta twice chanced his arm from distance and was not too far away the visitors started to prosper with skipper Dmitri Mikhailenko and Sergey Nazarenko prompting from the middle of the park.
However, just when it looked as though they had begun to gain the upper hand, they were undone by a piece of magic from Yakubu and Mendieta.
There looked to be little on when the Nigerian international picked up possession wide on the left after 36 minutes, but when he cut inside and laid the ball off for the Spaniard, the return pass was inch-perfect for him to blast past the helpless Artem Kusliy.
Kusliy denied the home side a second two minutes later when Mendieta sent a dipping shot in towards his near post, but by then, the balance of the game had swung in Boro's favour.
Boro returned knowing a second goal would effectively end Dnipro's hopes.
And they did not have long to wait as French referee Bertrand Layec employed the advantage rule to good effect after Mendieta had been upended on the left by Nazarenko. The ball ran to Viduka, who was given time and space to pick his spot and blast a right-foot shot past Kusliy into the top corner.
Two became three within five minutes when youngster James Morrison, who had earlier forced a good save from Kusliy, did the same again, but this time the ball fell to Viduka, who guided the ball into the empty net.
MIDDLESBROUGH: Schwarzer, Bates, Riggott, Queudrue, Parnaby, Mendieta (Kennedy 60), Doriva, Morrison, Pogatetz, Viduka (Nemeth 64), Yakubu (Maccarone 57).
DNIPRO: Kusliy, Shershun, Radchenko, Shelaev, Yezerskyi, Rusol (Lisitski 58), Semochko, Rykun, Mikhailenko (Motuz 66), Nazarenko, Kostyshyn (Melaschenko 52).
Referee: Bertrand Layec (France).