With the International Olympic Committee vote on whether Istanbul, Madrid or Tokyo will host the 2020 Olympics due on September 7, the timing of the announcement delivers another body blow to the tarnished image of Turkish sport.
Earlier on Wednesday, the Turkish Athletics Federation handed a two-year suspension to double European 100m hurdles champion Nevin Yanit for drugs violations, just weeks after similar bans were given to 31 other local athletes.
Playing under appeal against the original ban, Fenerbahce were beaten 2-0 by Arsenal in the second leg of a Champions League play-off on Tuesday, losing the tie 5-0 on aggregate.
Normally a defeat at this stage would still guarantee a berth in the continent's second tier competition but Fenerbahce will be barred from the Europa League following the CAS ruling.
Lausanne-based CAS said in a statement it had dismissed appeals filed by Fenerbahce and Ukraine's Metalist Kharkiv, barred by UEFA over involvement in a domestic match-fixing case dating back to 2008.
"Fenerbahce SK is excluded from two editions of the UEFA club competitions," CAS said in its ruling following a two-day hearing held at its headquarters on August 21-22.
Fenerbahce and fellow Istanbul club Besiktas were banned in June after a protracted UEFA inquiry into scandals that emerged in 2011. Besiktas, banned for one season, also appealed to CAS and its ruling is expected on August 30.
In a separate statement, UEFA said it welcomed the rejection of Fenerbahce's appeal.
Europe's governing body said the UEFA Emergency Panel would meet on Thursday to decide on the consequences the confirmed exclusion of Fenerbahce from the 2013-14 UEFA club competitions would have on the UEFA Europa League.
Fenerbahce, who won the 2010-11 title, were withdrawn from the following season's Champions League by the Turkish Football Federation as a result of their investigations into widespread match-fixing allegations that rocked the Turkish game.
Fenerbahce were implicated in the scandal with suspicions raised over their 4-3 victory against Sivasspor which clinched the league championship on the final day of the season.
Besiktas were implicated as a result of their involvement in the 2011 Turkish Cup final, which they won on penalties after a 2-2 draw against Buyuksehir Belediyespor.
Last July, a Turkish court convicted 93 defendants, including Fenerbahce chairman Aziz Yildirim, club executives and players, in connection with the case.
Yildirim was sentenced to more than six years in prison but was released from custody after launching an appeal, which is still proceeding.