Authorities have captured a suspect after locking down part of the city and launching a manhunt for the attacker amid fears of more attacks.
"A person who could correspond to the description given by the initial witnesses has been placed in police custody," Lyon's public prosecutor Nicolas Jacquet said in a report, adding that the suspect had not been carrying a weapon when he was caught.
The Christian clergyman, who is said to be a 52-year-old Greek citizen, is in the hospital with fatal injuries after being hit in the abdomen, a police official told.
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The man was locking up his church when a gunman struck at around 4pm on Saturday.
Police cordoned off the largely suburban neighborhood around the church and informed the public on social networks to stay away.
Bystanders to the attack on the 52-year-old, who has been in France since 2012, said they heard the sound of two gunshots and then the sound of a woman shrieking.
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It is believed that the woman's screams prompted the attacker to escape. The gunman was described as "male and in his forties" armed with a sawn-off hunting rifle. He is believed to have fired his weapon twice.
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The church where the priest tended is well known to the sizable Greek community in Lyon.
It is thought that there were no guards outside the Church, as there are at other Christian places of worship in France.
The victim is an Archpriest, a name used in Eastern Christian religions to represent a non-monastic priest, who was easily identifiable as a member of the priesthood because of his distinctive religious attire.
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The reason for the shooting was unclear, Lyon Mayor Gregory Doucet told reports on Saturday.
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It follows an attack at a church in Nice on Thursday in which three people were killed and comes amid high tensions between France and the Muslim world over comments made by French President Emmanuel Macron in defense of provocative cartoons depicting the Prophet Mohammed.
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French anti-terrorist authorities were not investigating Saturday's shooting, although the interior minister activated a special emergency team to follow the case while the gunman was still fleeing.
Following the attack, French Prime Minister Jean Castex said: "This is a very serious incident. Details are still emerging. A crisis unit has been set up."
Castex later reiterated government guarantees to place military forces at religious sites and schools.
He said French people can "count on the nation to allow them to practise their religion in full safety and freedom".
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