Kouri Richins was convicted in March of aggravated murder for lacing her husband Eric Richins' cocktail with five times the lethal dose of fentanyl at their home near Park City, Utah, in 2022.
A jury also found her guilty of four other felonies, including insurance fraud, forgery and attempted murder for trying to poison her husband weeks earlier on Valentine's Day with a fentanyl-laced sandwich.
Judge Richard Mrazik said Richins is "simply too dangerous to ever be free" when handing down the sentence on Wednesday, US time, the day her husband would have turned 44.
Her lawyers said they will appeal the conviction and sentence. Richins has been adamant in maintaining she is innocent, saying the verdict was "an absolute lie".
Richins stood at the podium in a lime green jail uniform as she asked her sons, who were not present in court, "Please just don't give up on me." She encouraged them to always "be like your dad".
Prosecutors said Richins, a 35-year-old real estate agent with a house-flipping business, was millions in debt and planning a future with another man.
She had opened numerous life insurance policies on her husband without his knowledge and falsely believed she would inherit his estate worth more than $US4 million ($A5.5 million) after he died.
Eric Richins' father, Eugene Richins, had urged Mrazik to impose a life sentence without the possibility of parole to protect his grandsons, who were ages nine, seven and five when their father died.
"This sentence is important so Eric's three sons never have to live with the fear that the person responsible for taking their father could ever harm them again," he said.
The case captivated true-crime enthusiasts when Richins was arrested in 2023 while promoting her children's book about a boy coping with the death of his father.
Richins' sons "are not props for some twisted children's book about grief and loss, and yet that is what they've been reduced to by Kouri", said her sister-in-law Katie Richins-Benson, who now has the boys in her care.
Social workers read letters from the sons, who all said they would feel unsafe if their mother was ever released from prison.
The children said Richins threatened to kill their animals and showed them videos of famished children in war zones when they refused to eat undercooked food.
"You took away my dad for no reason other than greed, and you only cared about yourself and your stupid boyfriends," said the middle son, now 11.
The jury deliberated for just under three hours before finding Richins guilty of all counts.