The former Real Madrid and Brazil coach, who had been in charge since October 2010, overcame internal squabbles to steer Flamengo to a 2-0 home victory over Real Potosi of Bolivia on Wednesday for a 3-2 win on aggregate in their preliminary round tie.
Luxemburgo said after Wednesday's win that he would be staying on in the job despite media speculation he was on his way out regardless of the result, but club president Patricia Amorim said the sacking was decided on Thursday.
"The decision about Luxemburgo was taken after the talk I had with him today," Amorim said.
"It had already been agreed with the coach that we would talk after the game but no decision was taken before that," she told a news conference at Flamengo headquarters.
"We listened to the opinions of the players, the fans and saw this was the right moment to make changes."
Santana, who has been coaching Bahia since September, handed in his resignation to the northeastern club on Thursday night according to the club's website, at the same time as Flamengo were announcing Luxemburgo's departure.
With the signing of former FIFA World Player-of-the-Year Ronaldinho from AC Milan in January last year, Brazil's most popular team expected a successful campaign but only won the low-key, early season Carioca [Rio] state championship.
Luxemburgo, who had a contract until the end of this year, also had problems with Ronaldinho due to the player's love for partying during the summer off-season in January.
A 2-1 loss to Real Potosi in the first leg of the Libertadores Cup preliminary round tie last week despite a week spent in Bolivia acclimatising to the high altitude virtually sealed Luxemburgo's fate even though his team qualified on Wednesday.
