Police said the crash happened on North Western Avenue between West Balmoral and West Catalpa avenues just after 3:45 a.m.
A 51-year-old man was driving his motorcycle southbound when he lost control and crashed, police said.
He was transported to St. Francis Hospital, where he was pronounced dead. His identity was not immediately released.
No one else was hurt, and CPD's Major Accidents Unit is investigating.
Police did not immediately provide further information about the crash.