The plane with the 26-year-old pilot Pavlo Ivanov was shot down on Saturday, according to a statement from the Ukrainian army.
"He was killed in battle, while defending his homeland from the invaders", it says in the statement.
The US-made planes, donated by, among others, Denmark and the Netherlands, began to be delivered last summer. About 80 planes have been promised, but it is unclear how many have been delivered so far.
In March, Ukrainian President Volodymyr Zelensky announced a new delivery without giving an exact number.
Only weeks after the first delivery, one of the planes crashed during an operation against a Russian air raid. According to the AFP news agency, Saturday's incident is the second involving an F-16.
Ukraine has not provided further details about Saturday's downing. In a post on X, Zelensky writes that the circumstances are under investigation.
Saturday night, several Ukrainian cities were shaken by explosions. At least three people were injured in Russian drone attacks on Kyiv, according to Mayor Vitalij Klytjko, and drones also struck in the eastern Ukrainian city of Charkiv.
Explosions were also heard in the Ukrainian port city of Odessa, according to the city's mayor.
In total, Russia sent 88 drones against Ukraine during the night, according to the Ukrainian air defense later on Saturday morning. 56 of them were shot down, according to a statement.
