Police were called to Kirkstall Road at 11.25pm on Monday after a silver Volkswagen Golf was involved in a collision with a man on a bicycle.
The cyclist, 33, was pronounced dead at the scene.
The 22-year-old driver of the car, which overturned causing damage to two shops on Kirkstall Road near the Cardigan Fields complex, was rushed to hospital.
He was this morning in a stable condition in intensive care at Leeds General Infirmary.
Kirkstall Road remained closed for much of the day but reopened around mid-afternoon.
The collision reportedly caused damage to shops on the road.
Road closures are now in force on the road following the crash and commuters have faced rush hour disruptions this morning.
Tony Woodrup, who owns the Woodrup Cycles shop opposite the buildings that were damaged, said: “The traffic is chaos everywhere.
“I walked down Kirkstall Road but it’s absolutely gridlocked.”
He said two shops across the road, cordoned off by police, had been damaged after collision.
Mr Woodrup added: “The police have got it all cordoned off but the front of the premises doesn’t look great.”
Police said a Volkswagen Passat car is also believed to have been involved in the incident.
Two men, aged 23 and 36 from Leeds who were inside the car, have been arrested and remain in custody.
The collision has caused disruption for commuters travelling towards the city centre today.
Closures have been in place on Kirkstall Road while police investigations are underway.
Police said the closures will remain “for some considerable time”.
Detective Chief Inspector Stuart Spencer, investigating, said: “This is clearly a very serious incident that has resulted in a man’s death and we are carrying out extensive enquiries to establish the full circumstances.
“A scene is currently in place in Kirkstall Road and will be undergoing detailed forensic examination throughout the day. Work is also ongoing to make safe the shop premises that were damaged. We expect the scene to remain in place for some considerable time.
“There will be significant disruption to traffic in the area. Diversions are in place and we would advise people to seek alternative routes and avoid the area as much as possible.”
Anyone information about the crash, or either cars, is asked to contact police on 101, quoting log number 1843 of November 14.