The 63-year-old man, who has been identified as Fritz N., was driving his BMW SUV with his second wife Stanila N. in the passenger seat.
The 43-year-old shot her husband dead at around 7pm while he was driving, daily newspaper Bild reported on Wednesday.
The car swerved into a wall, Fritz N. staggered out and collapsed onto a road in Tübingen's wealthy Denzenberg suburb, where the pair lived. Paramedics pronounced him dead at the scene.
His wife was believed to have fled on foot, but was soon tracked down by the police, who are keeping her in custody. They do not yet know why Stanila N. shot her husband, or why she chose to do it when they were driving.
According to neighbours that spoke to Bild, Fritz N. had not been living in their home for some time, and when he did enter it was only when “accompanied by tough-looking friends.”
The area is still being searched for a murder weapon, which is believed to have been discarded somewhere in the streets of Denzenberg.