With Italy and England completing a strong-looking Group D, Costa Rica were expected to be the whipping boys even with star striker Suarez - still recovering from a knee injury - unable to take the field in Fortaleza on Saturday.
The game went to script initially as Costa Rica's defensive gameplan was ruined by Edinson Cavani putting Uruguay ahead from the penalty spot in the 24th minute.
However, the two-time world champions were then left stunned as their opponents counter-attacked with purpose and scored three second-half goals to spring a major surprise.
Joel Campbell and Oscar Duarte found the net in a stunning three-minute period, before substitute Marco Urena made the game safe in the closing stages.
With talisman Suarez seemingly too unfit to leave the bench, a stunned Uruguay were unable to avoid a loss that leaves their hopes of progression looking bleak. An injury-time red card for Maxi Pereira only served to compound their misery.
There were plenty of early warning signs as Uruguay struggled to break down their opponents' 4-5-1 formation; the first time they did, Diego Godin saw his stabbed finish ruled out for offside.
Their annoyance grew stronger soon after, too, as the usually-reliable Cavani missed a golden opportunity when volleying wide from a deflected Diego Forlan free-kick.
Costa Rica's failure to heed that warning proved costly as Junior Diaz hauled down Diego Lugano in the box from an identical Forlan set-piece.
Cavani made no mistake this time as he arrowed a penalty beyond the dive of Keylor Navas.
Yet Jorge Luis Pinto's side found a response, showing they had the attacking capabilities to match their defensive nous in a promising spell highlighted by Campbell firing narrowly wide with a fizzing strike from distance.
The underdogs were soon indebted to a stunning save from Navas, though, as he turned Forlan's deflected effort over just before half-time.
It was Navas' opposite number Fernando Muslera who had to be alert immediately after the break, keeping out Duarte's header from point-blank range.
He could do little moments later, however, as Campbell fired home a half-volley after fine work from Cristian Gamboa.
Things soon went from bad to worse for Uruguay, Duarte stealing in at the back post, albeit with a suspicion of offside, to head home another fine Gamboa delivery.
Dangerous pot-shots from Campbell and Bryan Ruiz threatened further damage, yet there was soon a warning flash at the other end Cavani forced a good reactionary stop from Navas.
Hopes of a Uruguay comeback were ultimately extinguished with six minutes remaining as Campbell's wonderful throughball freed Urena, who belied the tight angle by superbly sliding beyond the onrushing Muslera.
If that goal added further gloss for Costa Rica, the game's last flashpoint summed up Uruguay's evening as Pereira was sent off for a wild hack at the impressive Campbell.
