In keeping with tradition, the Queen officially declared the Games open after receiving the baton from the final relay runner, Victorian state governor John Landy, the second man to run a mile in less than four minutes.
"Tonight we celebrate the value of sport as a means of bringing together people of 71 nations and territories, and from a wide range of cultures, traditions and beliefs," the Queen said.
"It gives me the greatest pleasure to declare the 18th Commonwealth Games open."
About 80,000 spectators had crammed into the grand stadium for a two-and-a-half hour, multi-million-dollar production that ushered the Games into Australia's second largest city.
Thousands more people lined the banks of the nearby Yarra River, where a flotilla of illuminated surfboats and rainbow coloured barges sailed by.
An estimated global television audience of 1.5 billion was expected to tune in as more than 4,500 athletes from an eclectic group of nations marched into the stadium.
The Queen, dressed in gold and accompanied by the Duke of Edinburgh and Prince Edward, arrived in a black Rolls Royce to take her seat before the show began.
The ceremony traced the story of a young boy's imagination and featured a range of distinctively Australian themes, including a flying tram that descended from the stadium roof and various native animals.
England led the parade of nations with diver Tony Ally the first into the stadium. The assortment of teams that followed included the world's biggest democracy India to tiny pacific nations like Niue and Nauru, all bound by their ties to Britain.
Hosts Australia entered last, with walker Jane Saville carrying the flag.
The Commonwealth flag was raised, Australian swimmer Adam Pine read the competitor's oath and Dame Kiri Te Kanawa sang "Happy Birthday" to the Queen, who turns 80 next month.
The baton relay, which had criss-crossed the globe for the past year, was then carried into the stadium by Australia's most famous Aboriginal athlete Cathy Freeman, who lit the torch at the Sydney 2000 Olympics before winning gold in the 400 metres.
Freeman passed the baton to Ron Clarke, who lit the torch at the 1956 Melbourne Olympics, who in turn gave it to former Olympic champion Marjorie Jackson, who handed it to Landy.
Landy never won an Olympic title and was beaten to the four-minute mile by Roger Bannister but is forever remembered for a spontaneous gesture of sportsmanship when he stopped to check on a fallen competitor during a race that he eventually won.
Organisers would have been breathing a sigh of relief with a seamless opening ceremony that marked the start of 11 days of competition after 10 years of meticulous planning and more than A$1.1 billion (465 million pounds) in funding.
The Games, held every four years since 1930 with the exception of 1942 and 1946, have not been without controversy and critics have dismissed them as an imperial anachronism that has no place in the 21st century.
Although more than one million tickets have been sold, another 400,000 remain available and the prospect of a late rush is fading after the withdrawal of drawcards like Australian swimmer Ian Thorpe and English distance runner Paula Radcliffe.
A television poll, conducted a few hours before the start of the ceremony, showed more than one-third of Australians had no interest in the Games, but organisers were decidedly more upbeat.
"In my experience this is the best planning and preparation for any Games I've been involved in," the president of the Commonwealth Games Federation Mike Fennell told reporters.
The competition programme features 16 sports, including lawn bowls, netball and squash, that represent the eclectic range of interests in the commonwealth.