Unione Calcio Sampdoria was founded in 1946 by a merger between Sampierdarenese and Societa Andrea Doria where the first mentioned team dates all the way back to 1891 and the last 1895 Sampdoria can be tracked in a mix of the two teams aswell as the jerseys: blue-white and red-black. 

Quickly after the merger Sampdoria asked to play at the Stadio Luigi Ferrari, the same stadium as city rivals Genoa. The rivalry between these two has lasted ever since and the match between them is called the Derby della Lanterna. The first 20 years of their history the team saw themselves playing in Serie A with their best result an eigth place in 1960/61 before relegating to Serie B in 1966.

In 1979 the team was bought by Paolo Mantovani who wanted to take the team back to the top-flight and be a major factor in Serie A. They made the return in 1982 and soon hereafter they got success winning their first Coppa Italia trophy in 1985. They won it again in 1988 making way for them in Cup Winners' Cup where they lost the final 1-0 to Barcelona. The year after, 1990, however saw them win the trophy, after another Coppa Italia victory, by beating Anderlecht after extra-time. 

Sampdoria was on high run these years and crowned it with their so far only Serie A title in 1991. The team reached the European Cup final, only to being beaten by Barcelona once again 1-0. Two years later in 1993 though Paolo Mantovani died and his son, Enrico, took over. This was a major blow for the team where many prominent players left the following years, although making some impressive signings as Juan Sebastian Veron and Enrico Chiesa.

It all resulted in the team being relegated to Serie B for the second time in their history in 1999. The team once again came back to Serie A after a new president, when Riccardo Garrone bought the club in 2002. The year later the team returned to Serie A and has minor success since having their best season in 2009/10 where they ended as number 4.