In Republican-leaning Virginia, Democratic Lieutenant-Governor Tim Kaine defeated former Attorney-General Jerry Kilgore despite an 11th-hour visit to the state and a personal appeal from Bush.
In New Jersey, Democratic Senator Jon Corzine easily beat back a challenge from Republican businessman Doug Forrester that included an attack on the divorced Corzine from his ex-wife.
Dozens of US cities across the country also picked mayors on Tuesday and seven states voted on ballot questions, including California, where Governor Arnold Schwarzenegger has bet his sinking political capital on passing four initiatives.
In New York, billionaire Republican Mayor Michael Bloomberg stormed into a second term with an overpowering victory over Democrat Fernando Ferrer - the culmination of a campaign that will go down as the most expensive mayoral re-election in history.
With control of both chambers of the US Congress and 36 governorships at stake in 2006, both parties will scour the off-year election results for clues to next year's political climate and the long-term effect of Bush's plummeting approval ratings, now the lowest of his presidency.
The Virginia result in particular was a blow to Bush, who stopped in the state to attend a rally with Kilgore on his return from Latin America on Monday.