The club was founded on 30 May 1923 by the merger of Šk Čechie and ČšŠk into TSS Trnava. After a communist takeover it became affiliated with the metal industry and was renamed to TJ Kovosmalt ("Metal-enamel"). In 1952, the club gained its current name.
The Golden era of Spartak began in the 1966/67 season. The team of legendary coach Anton Malatinský was top of the league by the autumn, but by the end of the season had finished only in third place. Great success was achieved in the Mitropa Cup. Spartak beat teams like Budapest Honvéd FC, S.S. Lazio and ACF Fiorentina and in the final they defeated Újpest FC of Hungary. In the following season Spartak gained their most memorable European results. They reached the semi-final of the European Cup to face Ajax Amsterdam. It is their greatest success to date. Under the management of Ján Hucko, the team also won a second championship. In 1970/71 and 1971/72, Trnava won their third and fourth championship titles under coaches Valér Švec and Anton Malatinský. The team also reached the quarter-final of the European Cup in 1973 and 1974. The fifth and the last league title in 1972/73 beckoned the end of Spartak's golden era.
Although Spartak finished 16th (and last) in the last unified Czechoslovak league season in 1992/93, the latter half of the 90s can be considered the renaissance of football in Trnava. In the 1995/96 season, Spartak finished third and its popularity grew. The 1996/97 season was a memorable on for the fans of Spartak, Karol Pecze almost led the team to its first Slovakian league title but got beaten to it by Košice in the final week of competition. The following season, under new coach Dušan Galis the team again achieved second place and then third place in the 1998/99 season which saw the end of this recovery of footballing prowess in Trnava.
The fans are well known throughout the country for their passion. The main ultras group is called Ultras Spartak. They are universally considered to be the best fans in Slovakia. Trnava has had the highest average attendances in the republic for a long period of time.
Between 1988 and 2006, Spartak ultras had a mutual friendship with FC Baník Ostrava fans, good relations and friendship still exist to this day.
Traditionally, the club has great support in the city and its districts, but it is very popular in the whole western region of Slovakia, especially in the Hlohovec, Piešťany and Sereď areas.
Štadión Antona Malatinského is located in the centre of Trnava, directly behind the walls of the old town. It currently has capacity of 3,227 spectators, due to reconstruction. Formerly known simply as Spartak stadium, it was renamed in 1998 in honour of the club's most successful manager Anton Malatinský.