Zhao, who continues to defy expectations in Sheffield, made the brighter start.
The 28-year-old Chinese star, competing as an amateur this season following a return from suspension, showed no signs of nerves on his debut at the Crucible's single-table set-up.
He raced into a 2-0 lead with composed breaks of 60 and 62, hinting at his vast natural talent.
But O'Sullivan, ever the competitor and appearing in a World Championship semi-final for a record-extending 14th time, responded in typically ruthless fashion.
The seven-time world champion rattled in three successive half-century breaks to swing the momentum and establish a 3-2 advantage.
The remainder of the session saw both players exchange blows. Zhao recovered his composure with a classy 86 break - featuring a superb black down the right corner rail - to level the scores once more at 4-4 ahead of Friday morning's resumption (10:00 BST).
Their best-of-33 frame clash will continue across four sessions, with a place in the final on the line for both men.
While O'Sullivan chases a record eighth Crucible crown to cement his status as the sport's greatest modern player, Zhao is bidding to complete one of snooker's most extraordinary comeback stories.
Elsewhere, the other semi-final - featuring three-time champion Mark Williams and 2019 winner Judd Trump — is set to get underway later at 19:00 BST.