KYIV, Ukraine—President Volodymyr Zelensky is shaking up his government as he aims to bolster Ukraine’s military and political positions ahead of the U.S. presidential election.

Several Ukrainian ministers, including the country’s top diplomat, have submitted resignations as part of an overhaul that Zelensky said is designed to improve ties with the West and increase weapons production.

The shake-up, the biggest since the start of the war, comes as Zelensky is seeking U.S. backing for what he has called a “victory plan” aimed at pressuring Russia to halt its invasion.

Zelensky has said he plans to present the plan to President Biden and presidential candidates Kamala Harris and Donald Trump on a visit to the U.S. for the United Nations General Assembly at the end of September.

“Fall will be extremely important for Ukraine,” Zelensky said in his nightly address Tuesday. “Government institutions must be set up in such a way that Ukraine will achieve all the results we need.”

Two-and-a-half years into the war, Ukraine is facing a fraught outlook on the military and political fronts. Long-term Western support, which has sustained Ukraine’s resistance against its much-larger invader, remains uncertain as elections and domestic pressures loom in the U.S. and European Union members.

At the battlefront, Ukraine’s armed forces are suffering incremental losses in the east as Russia advances on the key logistics hub of Pokrovsk and presses at several other hot spots. Over the summer, Russia has continued to attack critical infrastructure with missiles and explosive drones, causing widespread blackouts across the country.

Ukrainian servicemembers in the northeast of the country. Photo: Emanuele Satolli for WSJ

Ukraine invaded Russia’s Kursk region in August, in part to gain leverage in any future talks, and Zelensky is seeking more weapons from the U.S. and its allies, as well as permission to use Western-supplied missiles to strike in Russia. The plan has already yielded some results, gaining some 500 square miles of territory and hundreds of Russian prisoners of war that Kyiv has started exchanging for Ukrainians held by Russia.

Zelensky told NBC News on Tuesday that Ukraine would hold territory in Kursk indefinitely as part of a victory plan but has no intention to keep it permanently.

“We don’t need their land. We don’t want to bring our Ukrainian way of life there,” Zelensky told NBC News.

Russia, meanwhile, has shown little interest in any peace deal other than a Ukrainian capitulation, and is advancing gradually on the battlefield in Ukraine’s east .

The Kremlin said Wednesday that Ukraine’s government reshuffle wouldn’t affect potential peace talks with Russia.

“It won’t have any effect whatsoever and it has nothing to do with the prospects of the negotiation process,” state news agency TASS cited Kremlin spokesman Dmitry Peskov as saying.

Dmytro Kuleba , Ukraine’s minister of foreign affairs, is the most prominent official to tender his resignation, in a letter posted to social media by the head of Ukraine’s parliament, Ruslan Stefanchuk . Spokespeople for Kuleba or Stefanchuk didn’t immediately respond to requests for comment.

During his 4½-year tenure, Kuleba has worked to build diplomatic ties with countries that haven’t been historically allied with Ukraine, in an attempt to boost Ukraine’s global standing. In July, Kuleba visited China —a key partner for Russia in weathering Western sanctions—in an attempt to seek Beijing’s support to end the war on “just” terms.

Several other ministers tendered their resignations Tuesday night, including the top government officials for justice, weapons production and integration with the West. David Arakhamia, the head of Zelensky’s political party, Servant of the People, said over half of the personnel in the cabinet of ministers would be changed.

“Tomorrow is the day of dismissals, and the day after tomorrow is the day of appointments,” he wrote in a statement on social media Tuesday.

Zelensky identified five top priorities for a new government, including improving relations with NATO, advancing Ukraine’s EU membership status and strengthening the country’s growing defense industry through foreign investments—a critical effort as Ukraine builds out its domestic production capabilities in the face of questions over the long-term sustainability of Western aid.

Kyiv hasn’t yet announced the replacements for the ministers who resigned this week. The resignations must first be confirmed by a majority vote in Ukraine’s parliament.

Russian missile-and-drone strikes, meanwhile, claimed more civilian casualties overnight, this time in the city of Lviv, located some 40 miles from Ukraine’s western border with North Atlantic Treaty Organization member Poland. Ukrainian officials said seven people, including three children, were killed. The attack follows a ballistic-missile attack Tuesday on a military institute in the central Ukrainian city of Poltava that killed at least 51 and injured more than 200.

Local residents in the wake of the Lviv attack. Photo: Serhii Korovayny for WSJ

The aftermath of a Russian assault on Lviv, western Ukraine, on Wednesday. Photo: Serhii Korovayny for WSJ

Kuleba hasn’t commented on his resignation, but posted a statement about the attacks, urging partners to provide Ukraine with the weapons it needs to fight back and use their own air defense to protect Ukrainians.

“Partner air defense can and must be used to protect civilian people in Ukraine,” he said. “Shooting down pieces of deadly metal in the air does not constitute a country’s participation in the war. The simple act of saving human lives cannot be considered an escalation.”