Audi released the C4 (a heavily revised C3) in 1991. The C3-platform Audi V8 continued to be sold as a separate line. The major change for the C4 was the introduction of a 2.8 L, 90-degree, SOHC 12v, V6 engine. It was later joined by a 2.6 L variant, of the same configuration as the 2.8 L unit. They are essentially the same engines offered in the 1992, B4 Audi 80. The option of quattro permanent four-wheel drive was an option across the range, and the Audi 100 quattro was available with a ZF four-speed automatic gearbox.

For the 1995 model year, in conjunction with some styling revisions, Audi dropped the Audi 100 tag, renaming it the A6 instead. In addition, the existing 100-derived Audi S4 became the S6. The S4 name was later re-used for the high-performance derivative of the Audi A4. The Audi V8 had been replaced by the A8 in 1994.

The C4-based A6 continued until early 1997, when it was replaced by an all-new A6.