The Lithuanian and his team set a time of 37 minutes and four seconds across the 33.2-kilometre course around Verona, beating nearest rivals Katusha by five seconds.
It was the Saxo Bank squad who rounded out the podium on a stage which produced a surprising set of results as a number of established squads struggled to register strong times.
Overnight leader Taylor Phinney (BMC Racing) was in difficulty out on course following a hard crash at the end of Tuesday's stage three, the American carrying heavy strapping on his ankle, even veering wide onto the grass at one point during the stage.
The result means that Garmin-Barracuda hold the top four places on the general classification with Navardauskas inheriting a 10-second advantage over team-mates Tyler Farrar and Robbie Hunter.
Good conditions greeted the riders as the race returned to Italy with an out-and-back course centred in Verona.
Katusha put in a superb time, laying down a strong benchmark of 37:09 with overall contender Joaquin Rodriguez in tow.
The day proved to be a disappointing one for Team Sky who could only manage ninth quickest time, 30 seconds back.
Mark Cavendish returned to action following his hard crash in Denmark and led the team into the finishing straight. Also in attendance was Geraint Thomas who slipped to seventh overall, 21 seconds down on the new leader.
Five seconds ahead of Team Sky were Orica-GreenEDGE, the Australian outfit recovering from a few dramas out on course including a lurid slide from Canadian Svein Tuft.
The action from the first Grand Tour of the season continues with stage five on Thursday which looks likely to end in a bunch sprint.