The girl, believed to be aged two, was taken to hospital at 3.20pm on Wednesday.
Bystanders rushed to the aid of the youngster until emergency services arrived.
A section of Nechells Park Road was sealed off for three hours as detectives investigated the circumstances of the collision.
The lorry driver stopped at the scene and is helping police with their enquiries.
A West Midlands Police spokesman said: "We are currently on Nechells Park Road, Birmingham after a toddler was hit by a lorry at 3.20pm today.
"The girl was rushed to hospital where she remains in a serious condition.
"Officers from our collision investigation unit are at the scene. We thank you for your patience as the road is currently closed.
"The lorry driver stopped at the scene and is assisting our enquiries."
Two ambulances, a paramedic officer and a critical care paramedic attended the scene.
The youngster was rushed to Birmingham Children’s Hospital for specialist treatment.
A spokesman for West Midlands Ambulance Service said: “Ambulance staff arrived on scene to find the pedestrian, a young girl, being cared for by bystanders following a collision with a lorry.
"The team of ambulance staff worked together to administer trauma care to the girl on scene before conveying her by land ambulance on blue lights to Birmingham Children’s Hospital for further specialist treatment."
Anyone with information can contact police by calling 101 and quoting log number 2380 of August 4.