Obama, as expected, carried the state's 11 electoral votes in the presidential race, handing Mitt Romney a defeat in his home state, where he served as governor for one term from January 2003 until January 2007.
Many voters clearly wrestled with the decision in the Senate race.
In Wayland, a western suburb of Boston, 53-year-old Bob Virzi said he picked Warren.
"It was a tough call," he said. "I just feel like we can't let the Senate go into Republican control. I like Scott Brown, but if you look at his record, it's not as clear-cut as it should be."
Virzi, an unaffiliated voter who describes himself as a semi-retired consultant, also voted for Obama, saying the economy was much better off than when he took office.
Lynda Connell, a 50-year-old registered nurse from Whitman, said she voted for Brown because she believed he was willing to work with Republicans and Democrats.
"He's very bipartisan, and he's voted on the issues, not just by the party," Connell said.
Connell said she voted for Romney for fiscal reasons.
"He's run a major company. I liked him when he was governor. I think he did a good job," she said.
Romney drew high security when he and his wife cast their ballots in suburban Belmont, which they still call home. They were then off to Ohio and Pennsylvania for last-day campaigning in key swing states.
Massachusetts Secretary of State William Galvin said mostly anecdotal reports around the state pointed to a strong turnout, with long lines at some polling places. He said he had received relatively few reports of major voting problems and most had been resolved.
In Billerica, for example, workers at a polling place became concerned that they might run out of ballots because the town apparently hadn't given them enough, Galvin said. A police car, lights flashing, was dispatched to deliver more ballots, and no one was denied a chance to vote.
"Nobody left. Everybody got their ballots," Galvin said. "It all ended happily."
Voters said yes to ballot Question 3, allowing marijuana to be used medically for people with cancer and other conditions.
Also approved was Question 1, which requires automakers to share diagnostic and repair information with independent mechanics.
Voters were also deciding Question 2, which would allow doctors to prescribe life-ending medication at the request of certain terminally ill patients.
The fiercest congressional contest was in the 6th District, where Republican Richard Tisei challenged Rep. John Tierney, who was hurt by a gambling scandal involving his wife. If Tisei wins, he would be the first Massachusetts Republican elected to the House since 1994. He has said he also would be the first openly gay Republican candidate elected to the House.
Democratic incumbents carried the day in the state's other House races.
Rep. Edward Markey, the dean of the state's congressional delegation, defeated Republican Tom Tierney in the 5th district; Rep. Niki Tsongas bested Jon Golnick in the 3rd district; freshman Rep. William Keating defeated Christopher Sheldon in the 9th district; Rep. Stephen Lynch bested Republican Joe Selvaggi in the 8th district; and Rep. Michael Capuano won over independent Karla Romero in the 7th District.
Rep. Richard Neal in the 1st District and Rep. James McGovern in the 2nd District were unopposed Tuesday.