Miguel Uribe Turbay, a member of the opposition right-wing Democratic Centre Party, was shot in the head and leg on 7 June.
The 39-year-old’s death was confirmed by his wife.
Santa Fe Foundation hospital, in the capital Bogota, said the senator died early on Monday, after it previously revealed his condition had worsened over the weekend.
The shooting happened during a political event at a park in the Fontibon neighbourhood of the capital.
A teenage suspect was arrested at the scene and authorities have since detained several other people.
Mr Uribe Turbay underwent multiple surgeries before his death.
In a social media post, his wife Maria Claudia Tarazona wrote: “I ask God to show me the way to learn to live without you.
“Rest in peace, love of my life, I will take care of our children.”
The incident has renewed concerns about the safety of politicians in the country.
The last time Colombians saw this kind of political violence against presidential candidates was when drug lord Pablo Escobar declared war on the state in the 1990s.
Mr Uribe Turbay’s mother, journalist Diana Turbay, was a victim in this period and died in 1991 during a botched rescue mission after she was kidnapped by the drug cartel.
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Despite his mother’s death when he was a boy, Mr Uribe Turbay later became a prominent public figure and enjoyed a rapid rise in politics.
He was known for his criticism of leftist President Gustavo Petro’s administration.
His maternal grandfather, Julio Cesar Turbay, was Colombia’s president from 1978 to 1982 – while his paternal grandfather, Rodrigo Uribe Echavarria, headed the Liberal Party and supported Virgilio Barco’s successful 1986 presidential campaign.