Dzeko scored either side of the half-time break to inspire Bosnia to victory against fellow FIFA World Cup participants Ivory Coast at Edward Jones Dome.
The Manchester City striker broke the deadlock just past the quarter-hour mark before making sure of the win eight minutes into the second-half.
Ivory Coast substitute Didier Drogba scored a stunning free-kick during the closing stages, though it was only a mere consolation.
It was a confidence-boosting win for Bosnia, who are set to face Argentina, Nigeria and Iran in Group F in their first-ever World Cup appearance.
Safet Susic's men had lost their last two competitive games prior to Friday's fixture but they now head into Tuesday's friendly against Mexico full of confidence.
As for Ivory Coast, it is back to the drawing board and quickly after three games without a win, with the African nation up against Colombia, Greece and Japan in Group C in Brazil.
A very open start at the home of NFL franchise the St Louis Rams saw Bosnia-Herzegovina with the better of the play before Dzeko's opening goal in the 17th minute.
Miscommunication in the Ivory Coast defence led to the ball falling to the Manchester City striker at the edge of the area.
With goalkeeper Sylvain Gbohouo having been drawn out by an attempted chest back, Dzeko was on hand to curl an effort into an open net for his 34th international goal.
Ivory Coast started to settle into the encounter midway through the first half, albeit without overly troubling Asmir Begovic's goal.
It was mostly from set-pieces that Ivory Coast, without Manchester City star Yaya Toure and his brother Kolo, looked threatening.
Bosnia continued where they left off after the break, doubling their advantage in the 53rd minute.
Miralem Pjanic delivered the ball to Dzeko on the edge of the box and the towering front man turned his defender before finding the back of the net with a half-volley to move 10 goals clear of team-mate Zvjezdan Misimovic in the scoring charts, though Gbohouo could have done better.
Ivory Coast almost found a way back into the contest on the hour-mark, however their effort was cleared off the line by veteran defender Emir Spahic.
The introduction of Drogba sparked Ivory Coast into action.
But as they attempted to reduce the deficit, it left them exposed in defence during the final half-hour.
Second-half substitute Vedad Ibisevic, who replaced man-of-the-match Dzeko, was at the centre of some decent chances for Bosnia.
But the Stuttgart striker could not get on the end of several delightful crosses into the penalty area.
Bosnia were by far the better team throughout but they were breached in the first minute of injury-time.
Drogba was fouled outside the box and the striker, who is a free agent after leaving Galatasaray, alerted potential suitors with a thunderous free-kick - his sixth goal in eight games for the national team.
Bosnia are back in action against Mexico in Chicago on Wednesday before flying out to Brazil for their opening World Cup match against Argentina on June 15.
Meanwhile, Ivory Coast are set to face El Salvador on the same day.
Ivory Coast go head-to-head with Japan in the opening game of their World Cup campaign on June 14.
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