Former European champions Greece were left sleeping comfortably on their hopes of making the finals in Brazil after beating Romania 3-1.
Meanwhile, Iceland's dream of becoming the smallest nation ever to qualify for the World Cup was left on a knife-edge after a 0-0 draw at home with Croatia.
France have it all to do in the second leg in Paris on Tuesday after defeat in Kiev meant they face missing out on the World Cup for the first time in two decades.
Roman Zozulia gave Ukraine a deserved lead in the 61st minute at the 70,000-capacity Olympic Stadium in Kiev and Andriy Yarmolenko made it 2-0 from the penalty spot with eight minutes left after Laurent Koscielny had brought down Zozulia inside the area.
Ukraine were worthy of their win and, having denied France an away goal, can now consider themselves strong favourites to go through to their second World Cup finals.
"We're not beaten yet, there's always hope," said France goalkeeper and captain Hugo Lloris. "We know we have enough quality to turn it around."
Ronaldo overshadows Ibrahimovic
At Lisbon's Stadium of Light, Ronaldo edged Zlatan Ibrahimovic in the battle of potential World Cup superstars, scoring a late diving header which gave Portugal a 1-0 win over Sweden.
The Real Madrid star headed past Sweden goalkeeper Andreas Isaksson in the 82nd minute from six yards out after a fine left-wing cross from Miguel Veloso.
But the Portuguese had to settle for a one-goal edge ahead of the second leg in Stockholm, where star striker Ibrahimovic will be key to helping Sweden to the finals in Brazil next year after a low-key performance on Friday.
"It was an important goal and it gave us victory," said Ronaldo. "We could have scored one or two more goals but this advantage gives us confidence for the second leg.
"Nothing is settled yet. It's 50-50. I cannot promise that we will qualify but I will do all I can to achieve it."
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Can Africa for the first time in brazil appear in the top four. Is there any antido to africa poor performance in previous world cup. Senigal, Ghana and some few african nations where proud of being eliminating at the round sixteen whiles Europe and south america see such as a poor performance on their behalf. can any african nation one also fell like this people. That is the question i always ask when any world cup approches