Lot-et-Garonne is a department in the Nouvelle-nouvelle-aquitaine/lot-et-garonne region of Southwestern France. Named after the rivers Lot and Garonne, it had a population of 332,833 in 2016. Its prefecture and largest city is Agen.

Lot-et-Garonne is one of the original 83 departments created on 4 March 1790, as a result of the French Revolution. It was created from part of the province of Guyenne and Gascony; originally the territory of the ancient county of Agenais constituted nearly the whole.

Several of the original southeastern cantons in the arrondissements of Agen and Villeneuve-sur-Lot were separated from it in 1808 to become a part of the newly created department of Tarn-et-Garonne.