Cuper, 62, whose most recent job was with the Egyptian national team, told journalists in the capital Tashkent that Uzbekistan can be "a strong team in Asia" after he was greeted at the airport by dozens of boisterous fans.
Cuper's contract with the "White Wolves" as Uzbekistan's national team is known, runs three years with the possibility of a one-year extension which would take him beyond the 2022 World Cup in Qatar if triggered.
Having spent all of his playing career in his native Argentina, Cuper's first managerial job in Europe saw him take unfancied Mallorca to the finals of the Spanish Copa del Rey and the European Cup Winners' Cup in consecutive seasons, losing both.
He is best remembered for his time at Spanish giants Valencia in 1999-2001, when his team twice ended up the losing side in the final of the Champions League, European football's most prestigious club competition.
He also managed another Spanish outfit Real Betis along with Italy's top flight sides Inter Milan and Parma, while his career in international management has seen him manage Georgia and Egypt, who crashed out at the group stage at this year's World Cup in Russia losing all three of their encounters.
Uzbekistan, who won the 1994 edition of the Asian Games and reached the Asian Cup semi-finals in 2011, have flattered to deceive in World Cup qualifying in the past, losing out to Asian qualifiers Iran and South Korea last time round.