The ceremony at Central Command headquarters in Tampa, Florida, also saw Abizaid promoted from lieutenant-general to general.
Defence Secretary Donald Rumsfeld said: “I know of no one more qualified to follow in Tom Franks’s very large footsteps.”
Abizaid, 52, will oversee troops in a region that encompasses 25 countries in the Middle East and southwest Asia, an area that spans some 5,000 km east to west and 5,750 km north to south.
The United States has about 250,000 troops in the region, including 145,000 in Iraq, another 9,000 in Afghanistan and about 1,500 in the Horn of Africa.
“I know of no one more qualified to follow in Tom Franks’s very large footsteps.” - Rumsfeld
"We know success (in the region) will require not only military muscle but the focus of economic, political, intelligence and diplomatic efforts of the United States and of our friends and allies," Abizaid said.
"We also know the ultimate success will rest in the hands of courageous Afghanis and Iraqis, which will lead their people to a better future."
Abizaid, a 1973 graduate of the US Military Academy at West Point, is said to be an expert in Arab affairs with a master's degree in Middle Eastern studies from Harvard University.
He also studied at the University of Jordan in Amman and was an operations officer with a UN observer group in Lebanon.
Abizaid previously commanded a group of elite Rangers into combat in Grenada in 1983, and more recently, US peacekeepers in Kosovo.
General Abizaid was given the nickname the "mad Arab" at the US military academy at West Point.
He has been a strong advocate of training troops in peacekeeping, as well as offensive roles. He will also oversee the withdrawal of US forces from Saudi Arabia.