The area was populated since the Middle Ages and Velikiye Luki was first mentioned in the chronicles under 1166.

On August 1, 1927, the uyezds were abolished, and Velikoluksky District was established, with the administrative center in the town of Velikiye Luki.

Pskov Governorate was abolished as well, and the district became a part of Velikiye Luki Okrug of Leningrad Oblast.

On January 29, 1935, the district was transferred to Kalinin Oblast, and on February 5 of the same year, Velikoluksky District became a part of Velikiye Luki Okrug of Kalinin Oblast, one of the okrugs abutting the state boundaries of the Soviet Union.

On August 22, 1944, the district was transferred to newly established Velikiye Luki Oblast.

[11] On August 1, 1927, Porechyevsky District with the administrative center in the selo of Porechye was created on the territories which previously belonged to Nevelsky Uyezd.

[11] On March 10, 1945, Podberezinsky District with the administrative center in the selo of Podberezye was established.

One railway connects Moscow via Velikiye Luki with Riga and runs in the east-west direction.

Another railway, running to the northwest, connects Velikiye Luki via Toropets and Ostashkov with Bologoye.

The M9 Highway, which connects Moscow and Riga, crosses the district from east to west.

The roads connecting Velikiye Luki with Novosokolniki, with Nevel, and with Porkhov via Loknya all cross the district.

[14] The federal monuments are the Korvin-Krukovsky Estate in the village of Polibino and ten archeological sites.