Pavlohrad, a logistics hub near the central city of Dnipro, was hit ahead of a much-anticipated counter-offensive by Ukraine.
The strike sparked a major fire, destroyed dozens of houses, and wounded 34 people.
Hours later, the air raid alert sounded across the country, with the capital Kyiv among the targets.
Across the country, the Ukrainian army said it shot down 15 of the 18 cruise missiles that had been fired.
The most significant damage was in Pavlohrad, a city in Ukrainian-held territory around 70 miles (110km) from the frontline. Pictures posted on social media showed a massive blaze.
One resident, Olha Lytvynenko, said she was getting dressed to leave their house when “both doors were smashed out by the explosion wave”.
“I ran outside and saw that the garage was destroyed. Everything was on fire, glass shards everywhere. Had we been outside, we would have been killed,” she said.
Ukraine’s Dnipropetrovsk military administration described it as a “tragic night and morning”, saying an industrial site had been hit.
Nineteen high-rise apartment blocks, 25 private houses, six schools and kindergartens and five shops were also damaged, it added.
Vladimir Rogov, a Russian-installed official, said the strike targeted railway infrastructure and fuel depots, in a message on Telegram with a thumbs-up gesture.
Hours later, at around 04:00 local time (02:00 GMT) the air raid alert sounded in Kyiv and lasted for about three hours.
The military administration said all missiles and drones directed at the capital were destroyed.
They came from ground-based weapons, as well as drones and planes, the authorities said, adding that one person was killed.
Recent days have seen an increase in attacks in Ukraine, with places away from the front lines being targeted. On Friday, 23 people were killed in the central city of Uman.
Ukraine says it is finishing plans for a long-awaited offensive against Russian forces, supported by Western-supplied weapons and military equipment.
Russia, meanwhile, is also preparing for a Ukrainian push, and has fortified its positions in occupied territory.
In the latest change at the country’s military leadership, Cl Gen Mikhail Mizintsev – the Russian deputy defence minister who oversaw armed forces logistics – has been sacked, after being appointed to the role only last September.
There have been longstanding complaints that front line troops are not getting sufficient military equipment, and suffer shortages of food and uniforms.
Meanwhile, a Ukrainian official on Monday said the army had ousted Russian forces from some positions in Bakhmut, an eastern city that has been under siege for months.
General Oleksandr Syrskyi, the commander of ground forces, said on Telegram the situation remained “quite difficult” – but “the enemy is unable to take control of the city”. Ukraine war : Russia launches second pre-dawn missile attack in three days Ukraine war : Russia launches second pre-dawn missile attack in three days Ukraine war : Russia launches second pre-dawn missile attack in three days Ukraine war : Russia launches second pre-dawn missile attack in three days IgMp