Devon Tims hasn't been seen since Tuesday night in the Humboldt Park community.
Police say the toddler might be with his 19-year-old cousin, Brian Connor, and a 16-year-old girl, Serna Lebron.
She was reported missing several weeks ago.
Tims is described as 3'5" tall and was last seen wearing a blue, brown and tan sweater and jeans. He has a birthmark on his left arm.
Anybody with information about the case is asked to call police.