Maine and Maryland have become the first US states to approve same-sex marriage by popular vote, while Washington state and Colorado set up a showdown with federal authorities by legalising recreational use of marijuana.
The outcomes for those ballot measures were a milestone for persistent but often thwarted advocacy groups and activists who for decades have pressed the causes of gay rights and drug decriminalisation.
"Today the state of Washington looked at 70 years of marijuana prohibition and said it's time for a new approach," said Alison Holcomb, manager of the campaign that won passage of Initiative 502 in Washington state.
Colorado governor John Hickenlooper, a Democrat who opposed legalisation, was less enthused. "Federal law still says marijuana is an illegal drug, so don't break out the Cheetos or gold fish too quickly," he said.
The results in Maine and Maryland broke a 32-state streak, dating to 1998, in which gay marriage had been rebuffed by every state that voted on it. They will become the seventh and eighth states to allow same-sex couples to marry.
In Massachusetts, where assisted suicide was on the ballot, supporters of a question legalising physician-assisted suicide for the terminally ill conceded defeat, even though the vote was too close to call.
A spokesman for the Death With Dignity Act campaign said "regrettably, we fell short." Massachusetts could have become the third state to allow terminally ill patients to get help from their doctors to end their lives with lethal doses of medication.
In another gay-rights victory, Minnesota voters defeated a conservative-backed amendment that would have placed a ban on same-sex marriage in the state constitution. Similar measures have been approved in 30 other states, most recently in North Carolina in May. Even though the amendment was defeated, same-sex marriage remains illegal in Minnesota under statute.
"The tide has turned - when voters have the opportunity to really hear directly from loving, committed same-sex couples and their families, they voted for fairness," said Rick Jacobs of the Courage Campaign, a California-based gay rights group. "Those who oppose the freedom to marry for committed couples are clearly on the wrong side of history."
The outcomes of the marriage votes could influence the US Supreme Court, which will soon consider whether to take up cases challenging the law that denies federal recognition to same-sex marriages. The gay-rights victories come on the heels of numerous national polls that, for the first time, show a majority of Americans supporting same-sex marriage. Barack Obama declared his support for legal recognition of same-sex marriage earlier this year.