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Santo André was founded on 18 September 1967, by people that wanted to have a team in their city representing the professional football of the Municipality.

The first Santo André directorship was elected on 4 October 1967, and was composed by the following members: Newton Brandão, the President; Wigand dos Santos, Antonio Ferreira dos Santos and Hildebrando Mota Carneiro, the vice-presidents; Nelson Cerchiari and Durval Daniel, secretaries; Matheus Guimarães Jr. and João Manha, the treasurers.

The first official match of the club took place on April 8, 1968, at Américo Guazzelli stadium in a friendly match against Santos. Pelé did not play, but watched the game and participated in the festivities. Santo André won 2 - 1.

In 1984 Santo André were invited to play in Série A based on their State Championship performance. The team reached the third round (ranked 10th overall), but were not invited to compete the following year as the criteria changed.

In 2003, Santo Andre finished as runners-up to Ituano in Série C and thus were promoted to Série B.

In 2004, Santo André won their first national title when they defeated powerhouse Flamengo in the Copa do Brasil final 4-2 on aggregate, gaining the right to compete in the following year's Copa Libertadores. Their first season in Série B was over before it started as the team was docked 12 points for playing an ineligible player. This meant at the time of the Copa do Brasil success their point tally on the local tournament was negative. The team recovered to comfortably avoid relegation.

In the 2005 Copa Libertadores, the team was eliminated in the group stage, finishing third, but recorded one of the biggest victories in the competition, a 6-0 victory against Venezuelan club Deportivo Táchira.

In 2008 Santo André were runners-up to Corinthians in the Série B and thus earned promotion to Série A. After a hard-fought campaign Santo André were relegated back to Série B on the last day of the season.

The 2010 Paulista State Championship proved to be a highly successful campaign. The team finished second in the table behind Santos after a mid season seven match winning streak put them in a commanding position. In the playoffs Santo André overcame Grêmio Prudente, before facing the all conquering Santos team who had scored nearly 100 goals already in all competitions. The first game ended in a 3-2 victory for Santos despite Santo André having a man sent off. The second match on 2 May 2010, proved to be an epic encounter as Santo André leveled the tie in the first minute, before being pegged back. A thrilling game finally ended 3-2 to Santo André (5-5 on aggregate) and saw three red cards given to Santos, and one to Santo André. Despite hitting the post twice, Santo André could not break down a professional Santos rear guard action. Santos thus won the title due to their superior overall record.

Santo André slipped into free fall and were relegated to Série C in 2010 and almost relegated to the Série D in 2011. Also in 2011, the club was relegated to the Campeonato Paulista 2nd division after a poor campaign had them in last place. In 2012, the team was relegated to Serié D for the first time in history, experiencing two relegations in three years. After being eliminated in the second phase of the Serie D in 2013, Santo André stopped competing in national competitions, because they were noit participating in the top state league, which has qualifiers for the Serie D.