Down 3-0 to Senegal at half-time, Uruguay battled back to draw 3-3 but it was not enough to prevent the South Americans from exiting the competition.
"With this match, an era ends. It's my decision," Pua said after the match.
The favourite to replace Pua is Nacional coach Hugo de Leon.
Pua stepped into the role in early 2001 after Argentine Daniel Passarella was dumped fromt he post.
He guided the side tot heir first World Cup since 1990 after they beat Australia in a play-off over two legs.
Before announcing his retirement Pua criticised Dutch referee Jan Wegereef for his handling of their final match.
There were two controversial penalty decisions - one for each side - and the over-officious referee issued 12 yellows - a record for a World Cup match.
"We should have had a bit more luck," said Pua.
"The first Senegal goal wasn't a penalty and our players were very disappointed with their performance in the first half.
However, the Uruguay coach did not put the sole blame for his side's exit on poor refereeing decisions.
He added: "I was proud of their efforts in the second half, unfortunately they couldn't win.
"We played against three very strong teams here and we will learn a lot from the experience we gained here."