The Premium brand Buick replaced the Regal model with the new LaCrosse in 2004 as a 2005 model year.
It had two V6 engines and front-wheel-drive. Despite its 4-speed automatic transmission offered as standard, it was fuel-efficient and thus it was the first vehicle to receive the SULEV (Super Ultra Low Emission Vehicle) title in 2006. The standard options were generous, and even a six-seats version was available. The base engine had 200 hp from a 3.8-liter displacement, while the CXS (highest trim) had 3.6-liter displacement and had 240 hp. The latter also was mated to a 4-speed automatic transmission.

Inside the cabin, there was plenty of room due to its big, 2.8 meter (110 in) wheelbase. Another plus point for the vehicle was the overall rating received from the IIHS, which placed the car amongst the top of its class. The CXS also had leather bucket seats, but on both trim levels, the heated seats were an option.

In the last production year, 2008, the LaCrosse received the 5.3-liter V8 small-block engine called LaCrosse Super. It was the fastest series Buick ever produced, with a 0 to 60 mph (0- 97 kph) sprint time in 5.7 seconds and a top speed of 240 kph (150 mph). In December 2008, the LaCrosse was dropped from production.