This is the best-known wine region in Germany. The ancient Mosel wine growing area supplied the powerful Roman city of Trier, and the area has never been without wine since. Vineyards are planted on both sides and all along the length of the River Mosel, though as always the warmer southern slopes are favored. The area includes five Bereich, with over half of all wine production sold under Grosslage names. There are approximately 60 Einzellagen of outstanding merit, of which over half are in Bereich Bernkastel.

The area's great wines come from excellent smaller estate bottlings. The middle Mosel grows the finest grapes, and all of its best wines are Riesling. The steep vineyards here are littered with decomposed slate, which helps conserve and reflect the sun's heat. Most Mosel Rieslings are made in traditional styles, medium-dry to medium-sweet, for charming, long-lived white wines. For bulk wines, there are great quantities of Mulller-Thurgau planted on the flatter, more fertile soils. The Mosel also has some remaining plantings of the ancient Roman Elbling vine; it makes light, refreshing simple wine with some local character.

Cooperative cellars are not very important here, as they vinify only about 20% of the vintage. The majority of the wine is bottled by individual estates (30%) and wine merchants (50%). Since the wine merchants deal with large German supermarket chains and also export a great quantity of wine, they have a strong influence on the wines ultimately offered on the market; simple QBA wines are often overcropped and the fine local character lost or diluted. In effect the venerable Mosel produces a huge amount of ordinary bulk wine and small amounts of great wines, but very little of medium grade.

The Saar River valley, whose harsh climate provides Riesling for Sekt and Eiswein almost every year, is also part of this region, as is the Ruwer valley. The Ruwer River joins the Mosel downstream from the city of Trier. It has a very small amount of land under vineyard (690 acres), and struggles to make fine Riesling wines in a challenging climate. In warmer years it produces distinguished dry and medium-dry dinner wines.