Yevhen Seleznyov broke the deadlock from the penalty spot in the second half and substitute Artem Kravets secured a crucial victory when he doubled the lead in the 87th minute to move Ukraine up to 19 points from nine games.
The odds on them finishing above Slovakia and claiming one of the two automatic qualification spots, however, will be stacked against them.
Ukraine host group winners and European champions Spain in their final encounter on Monday, needing to better Slovakia's result away in Luxembourg to finish in the top two.
Ukraine dominated possession but created little going forward before Romanian referee Ovidiu Hategan awarded the visitors a penalty for a handball when Macedonia defender Leonard Zhuta tried to block Andriy Yarmolenko's header at the far post.
Seleznyov fired home from the spot to open the scoring, before Sevilla winger Yevhen Konoplyanka failed to beat the keeper with a clear-cut chance in the 80th minute.
Kravets came off the bench in the second half to wrap up victory, bursting into the penalty area from the left and slotting the ball into the net between the keeper's legs.
"I am sure we would have broken the deadlock later in the second half even if I had missed the penalty," Seleznyov told broadcasters.
"I hope we can achieve a praiseworthy result with Spain."
Ukraine will have to do without centre back Yevhen Khacheridi and defensive midfielder Serhiy Sydorchuk for the game against Spain as both players were booked in the first half and will now serve a one-game suspension.
"These are very serious and unwanted losses," Ukraine coach Mykhaylo Fomenko told a news conference.
"We tried to explain that emotions should help, not destroy but failed put this idea into their mind.
"Both of them knew about a possible suspension before the match so now the players who step in against Spain have an opportunity to prove their worthiness."
(Reporting by Igor Nitsak; editing by Toby Davis)
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