Harrington was convicted by unanimous decision of a Central Criminal Court jury following a four-week trial.
The 38-year-old now faces a mandatory life sentence.
There were emotional scenes at the Angelsea Street courthouse in Cork as members of the families of both Karen Harrington and Santina Cawley reacted to the guilty verdict from the jury of seven men and four women following a harrowing four-week trial.
A twelfth member of the jury was discharged during the trial.
Santina's father, Michael Cawley, and mother, Bridget O'Donoghue, attended multiple days of the trial, which opened on April 25.
The trial – which also sat on May 6, what would have been Santina's fifth birthday – featured more than 40 witnesses.
Jury members viewed extensive CCTV camera footage, video-recorded Garda interviews with Karen Harrington as well as lengthy transcripts and detailed forensic evidence.
Karen Harrington also gave sworn evidence in her own defence – insisting she had not hurt or harmed Santina.
However, she was unable to explain how the child suffered critical injuries as well as bruises to almost every part of her body.
Santina died from a traumatic brain injury and severe spinal injury after suffering a complex fracture to her skull as well as fractures to her leg, arm and ribs.
Medical evidence was submitted that the injuries involved were unrecoverable.
The prosecution said the evidence showed the defendant was alone in the apartment with the little girl from 3.10am to 5.11am – with Karen Harrington's DNA on a blood spatter found on Santina's pink T-shirt and Santina's DNA found on a blood spatter recovered from a pair of adult female leggings discovered in a back bedroom of the apartment.
Jury members deliberated on a verdict for an hour and fourteen minutes on Friday before resuming their deliberations today.
Mr Justice Michael McGrath had acknowledged that evidence in the trial over its 13 days at hearing had been both harrowing and very difficult to listen to.
Sean Gillane SC, for the State, argued that the evidence including forensics, CCTV footage and witness statements all clearly pointed to Karen Harrington.
Defence counsel, Brendan Grehan, said it was "an awful crime", "a harrowing case" with "horrible" details for the jury to hear.
However, Mr Grehan said the defendant was adamant she did not harm the child – but could not explain who did.
"The fact that she cannot explain what happened is not enough (for a conviction)," he argued.
"She says she does not know what happened. What she does say is she did not do this and she could not do this. Karen Harrington does not accept that she is responsible for inflicting these injuries."
Harrington, of Lakelands Crescent, Mahon, Cork had denied the murder and insisted throughout her four-week trial that she did not hurt or harm the toddler.
In July 2019, she was involved in a sexual relationship with Michael Cawley, who was separated from his wife, Bridget, who was the mother of his five children.
His youngest child, Santina (2), was in his care.
The trial heard that Mr Cawley and Santina would often stay over at Karen Harrington's flat at No 26 Elderwood Park.
On July 4, Karen Harrington was socialising and drinking with her friend and neighbour, Martina Higgins, by the Atlantic Pond, a short walk from the Elderwood complex.
The duo were drinking and also smoked some cannabis. Both later met up with Michael Cawley and Santina.
Alcohol was purchased and they all returned to the flat shared by Ms Higgins with her partner, Eric Okunala in Elderwood.
All except Mr Okunala proceeded to drink until a row erupted between Mr Cawley and the defendant shortly before 1.30am.
Karen Harrington became very distressed and returned to her flat alone.
Mr Cawley later returned to her flat at 3am after having a row with Mr Okunala, who insisted the drinking party be brought to an end.
After placing Santina on a duvet, Mr Cawley left the apartment to walk into Cork city centre to look for a Limerick-based cousin.
Mr Cawley said Karen Harrington had agreed to care for his daughter while he was gone.
The trial heard he trusted the defendant with his daughter – and thought there was a great relationship between the two.
However, when he returned at 5.11am he discovered Santina lying naked and blood-spattered with critical injuries.
Karen Harrington fled the scene when challenged about precisely what had happened to the child.
She ran barefoot from the scene in the direction of Blackrock only to return accompanied by a friend within the hour.
Mr Cawley raised the alarm, screaming throughout the complex that his baby had been smothered.
The trial heard that gardaí called to the Elderwood complex three times in the space of two hours in the early hours of July 5 – the third and final time when Santina was discovered critically injured.
During evidence, numerous witnesses spoke of Karen Harrington screaming and roaring both in her flat and outside her flat after 3am.
She was opening and slamming closed the sliding door of her apartment with such force that the door eventually came off its runners.
Her next door neighbour, Dylan Olney, said he was "creeped out" by her behaviour in the early hours of July 5.
Mr Olney rang the gardaí after becoming concerned at the sound of a child crying within the defendant's apartment.
He told the trial he heard what sounded like a child being taunted and mocked – with the child's crying becoming steadily louder.
Mr Olney said he was concerned at what was going on and decided to contact gardaí.
However, when officers called to No 26 accompanied by Mr Olney shortly after 4.52am, there was total silence from within the flat.
After being unable to get any response from someone within the flat, gardaí departed – only to be called back to the flat just 15 minutes later when Mr Cawley returned to discover his child lying naked and critically injured on the duvet.
Gardaí and paramedics battled to stabilise Santina's condition at the scene.
The child was rushed to Cork University Hospital (CUH), where she was pronounced dead three hours later.