It happened at about 9.15am today (Thursday) in Park Row, at the junction with The Headrow.
The 51-year-old pedestrian was rushed to hospital for emergency treatment and is in a serious condition.
Park Row is closed and buses are taking diversions, causing delays to several services.
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A spokesperson for West Yorkshire Police said: "At 9.16am today, police were called to a road traffic collision involving a male pedestrian and a bus in Park Row, Leeds.
"The 51-year-old man was taken to hospital by ambulance for emergency treatment and is in a serious condition.
"A scene and road closure remains in place in Park Row."
Anyone who witnessed the incident is asked to contact West Yorkshire Police on 101 quoting log number 419 of August 26.
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