Letby, 33, murdered the five baby boys and two baby girls at the neonatal unit of Countess of Chester hospital in northern England over 13 months from 2015, injecting the infants with insulin or air, or force fed them milk.
Some of those she attacked were twins - in one case she murdered both siblings, in another she killed two of three triplets, and in two instances she murdered one twin but failed in her attempts to kill the other.
"This was a cruel, calculated and cynical campaign of child murder involving the smallest and most vulnerable of children," said the judge, James Goss, who sentenced her to life imprisonment with no prospect of release.
"There was a deep malevolence bordering on sadism in your actions... You have no remorse. There are no mitigating factors... You will spend the rest of your life in prison," he said as the parents of the babies sobbed in the courtroom.
Whole life orders are very rare, and only three women in the UK have received such a sentence before, including serial killers Myra Hindley and Rosemary West.
Police have found no motive for her crimes and Goss said only Letby knew the reasons for her actions.
She refused to leave the cells to hear her sentence being handed down, leading to demands that criminals must be forced to hear the effect of their actions on their victims or their families.
The mother of one of the victims described it as a final act of wickedness.
The harrowing crimes committed by Letby, who was in her 20s when she carried out her killing spree at her workplace, have horrified the UK, wrecked the lives of victims' families and caused lasting damage to her colleagues.
She was found guilty last week of seven counts of murder and seven of attempted murder following a 10-month trial at Manchester Crown Court.
Jurors were unable to agree on whether she had tried to kill six and acquitted her of two other charges of attempted murder.
Earlier the court heard emotional, heart-wrenching statements from each of the parents of those she murdered and tried to kill, recounting the trauma and "excruciating agony" she had caused.
"Lucy Letby has destroyed our lives. The anger and the hatred I have towards her will never go away," the father of the triplets said in a statement.
A mother of twins, one of whom was murdered while the other survived, said she hoped Letby lived a long life, spending every day suffering for what she had done.
"My family will never think of you again. From this day, you are nothing," the mother said.
Prime Minister Rishi Sunak said her failure to hear the impact of her actions first hand was "cowardly".
While the current law says judges can increase jail terms on those who fail to appear, the government is considering making attendance compulsory.
"That's something that we'll bring forward in due course," Sunak said.
The government has also ordered an inquiry into the case amid accusations from senior doctors on the neonatal unit that their concerns about Letby were not heeded by hospital bosses, with calls to ensure it is led by a judge who can compel witnesses to give evidence.
