The accident happened at The Centre roundabout in Cornwall Way, East Kilbride, at around 1.30pm yesterday.
The 91-year-old man, who was driving the Ford Fiesta, and his 86-year-old wife were freed from the vehicle by paramedics and taken to Hairmyres Hospital in the town.
The woman died a short time later and her husband remained in a serious condition in hospital, police said.
East Kilbride Bus Station was closed temporarily while emergency services attended the scene and there was heavy congestion in the surrounding streets for several hours as the road was closed off and investigations were carried out.
No other vehicles were involved in the collision and officers have appealed for witnesses.
Constable Ann Alexander said: "The roundabout is near the bus stop and is a busy area for traffic. I would ask that anyone who saw the crash or who has any information that will help with our enquiries, contact officers at Motherwell."