Democrat Tim Kaine defeated former attorney general Jerry Kilgore in Republican-leaning Virginia, despite Mr Bush's 11th-hour appearance on Mr Kilgore's behalf.
Democratic Senator Jon Corzine beat Republican businessman Doug Forrester in a New Jersey race, despite a bruising media attack on Mr Corzine by his former wife.
Republican mayor Michael Bloomberg was re-elected to a second term in New York, as dozens of cities selected their mayors.
Mr Bloomberg, a billionaire and founder of the media group that bears his name, reportedly spent as much as $US100 million ($A136 million) of his own fortune to defeat Democrat Fernando Ferrer, the Bronx borough president.
Californians are currently voting on four proposals by Governor Arnold Schwarzenegger, on which he has bet his sinking political capital.
With control of both chambers of the US Congress and 36 governorships at stake in 2006, the off-year election results offered grim news for Republicans looking for clues as to the political mood of the nation ahead of the mid-term elections, and the long-term effect of Mr Bush's plummeting approval ratings, now the lowest of his presidency.
The result in Virginia was a particular blow to the president, who stopped by the state to make a personal appeal to voters to choose Mr Kilgore, on his way home from Latin America.
With nearly 90 percent of votes in, results showed Mr Kaine took 51 percent of votes, and Mr Kilgore on 47 percent.
Mr Bush's mounting political problems and Mr Kilgore's poor showing could make Republicans hesitant to call on him for help next year.
Spiteful wife
Jon Corzine won in Democrat-leaning New Jersey, despite the airing of an advertisement featuring the published comments of his ex-wife.
She told the New York Times the divorced Mr Corzine "let his family down, and he'll probably let New Jersey down, too."
Mr Corzine, a multimillionaire and former Wall Street executive, replaces former Governor James McGreevey, who resigned last year after revealing a homosexual affair with an aide.
As governor, he will appoint his replacement as senator.
In Wednesday's most closely-watched ballot, Californians are voting on whether to adopt four referendum issues that former movie star Governor Schwarzenegger hopes will reinvigorate his faltering leadership.
He campaigned heavily for the four ballot initiatives, which were among 39 measures facing voters in seven states on issues ranging from gay rights to election reform.
A bad result could damage his bid for re-election next year.
Key mayoral elections have also been held in Detroit, Michigan; San Diego, California and Atlanta, Georgia, among other cities.
Balloting is always held on the Tuesday after the first Monday in November, as decreed by Congress in 1845.