is a Paraguayan professional footballer who plays as a striker for Paraguayan Primera División club Libertad. He is the record goal scorer and has earned over 100 caps for the Paraguay national team, thus he is regarded as one of the best players in the nation's history. Santa Cruz has scored goals at a professional level in each of the last four decades.

Santa Cruz started his career with Olimpia, progressing through their youth system to the first-team squad where he made his debut at the age of 15 in 1997. He finished his career with the club having scored 13 goals in 24 Primera División appearances where Olimpia claimed the 1997, 1998 and 1999 Primera División titles. Santa Cruz scored three goals in four appearances for Paraguay at the 1999 FIFA World Youth Championship before debuting for the Paraguay national team at the 1999 Copa América, where he scored three goals in four appearances. He immediately joined Bundesliga club Bayern Munich in August 1999 for a fee of €5 million, which was the highest transfer fee in Paraguayan football until 2019. where he scored five goals in 28 league appearances in his first season. He faced a series of injuries and heavy competition from teammates Giovane Élber, Roy Makaay and Claudio Pizarro which limited his impact and restricted his appearances for the club.

Santa Cruz was part of a successful team for Bayern, winning numerous Bundesliga, DFB-Pokal and DFB-Ligapokal titles. He also won the 2000–01 UEFA Champions League and the 2001 Intercontinental Cup. He left Bayern Munich in July 2007 to join Blackburn Rovers for a transfer fee of €5 million, where he scored 19 goals in the 2007–08 Premier League season. In June 2009, he joined Manchester City for a fee of £17.5 million on a four-year deal. Since his transfer, he was loaned out to Blackburn and Real Betis.

He represented Paraguay at the 2002, 2006 and 2010 FIFA World Cup tournaments, and at the 1999, 2007, 2011 (where Paraguay finished runners-up) and 2015 Copa América tournaments. He retired from international football in 2016, but reversed his decision in May 2019.