Guillen agreed to a four-year contract reportedly worth $10 million.
"It's a big step in my career, a new chapter," said Guillen, who was released from his contract with the Chicago White Sox after Monday's game.
A fiery competitor, the 47-year-old Guillen takes over a franchise that will be moving into a new ballpark in 2012 as the Miami Marlins.
"I hope fans are going to be excited for new era of the Marlins...I want people in Miami to be happy and excited about this ball club," Guillen said.
The Venezuela native was the Marlins' third base coach in 2002-03.
After the Marlins won the 2003 World Series, Guillen was hired to manage the White Sox. He compiled a 678-617 record during his tenure with Chicago, including a 78-82 mark this year. Guillen guided the White Sox to a World Series title in 2005, and was named the American League Manager of the Year in the process.
"This is a man with great passion and great energy. This is what this club needs. We needed more energy here," said Marlins owner Jeffrey Loria.