He came to international attention playing for the Slovakia Under-20 team in the 2003 FIFA World Youth Championship. On 3 September 2010, Hološko scored a last-minute goal against Macedonia after a Marek Hamšík assist to help provide a winning start to Slovakia's Euro 2012 qualification campaign.
At the mid of 2007/08 season, he was transferred to Beşiktaş JK in exchange of the forward Burak Yılmaz (a promising youngster at the time) along with veteran defender Koray Avcı plus a considerable sum of €5 million. Regarding the huge amount paid, and two first team regulars given to an exchange deal, both Yıldırım Demirören and the Beşiktaş board were severely criticized by media pundits. However, Hološko managed to blend in after a brief period of time and embarrassed many, with his miraculous performance during the 2008-09 season. Holosko is also well known for his goal against Fenerbahce in the second half of the season; he took the ball from his own half and later he ran through five Fenerbahce players and scored. He also scored a goal in the Turkish Cup Final in İzmir Atatürk Stadium vs Fenerbahce, with a final score of 4–2 to the Black Eagles.
After a prominently successful season, Holosko had to struggle with a heavy injury on his splint bone, which occurred in the CSKA Moscow-Besiktas Champions League game (the outcome of which was a 2–1 defeat to Besiktas). At the end of the first half of the 2009-10 season he had only made 5 league appearances, scoring just a single goal. On 2 December 2010 he scored Beşiktaş' 100th goal in UEFA Cup Competitions vs CSKA Sofia.
On 20 July 2015, Sydney FC announced that it had signed Hološko as the club's international marquee on a 2-year deal.
Whilst Sydney struggled in 2015-16, Holosko was a highlight and a fan favourite. His work ethic, speed, and goal scoring ability was much appreciated by the Sydney faithful.