The Atletico Madrid star sustained the injury during the Super Eagles' 3-1 victory over the Taifa Stars at the Godswill Akpabio International Stadium in Uyo on Friday.
Lookman, who provided the assist for Alhassan Yusuf's second-minute opener, was forced off in the 44th minute after experiencing discomfort in his knee, with Moses Simon replacing him.
Following further medical examinations, the Super Eagles media confirmed on Saturday that scans had revealed a ligament sprain, ruling the forward out of the return fixture in Zanzibar.
"Scan has revealed Ademola Lookman suffered a sprain in his knee ligament during yesterday's match. This rules him out of Nigeria's next AFCON qualifier versus Tanzania in Zanzibar on Tuesday," media officer Promise Efoghe confirmed to Flashscore.com.
The 29-year-old is expected to return to Spain for further assessment and treatment, although the duration of his absence remains uncertain.
His injury represents another setback for head coach Eric Chelle, who is already without Galatasaray striker Victor Osimhen, following a knee injury that required surgery.
Despite Lookman's premature substitution, the three-time African champions survived a scare in the Akwa Ibom state capital thanks to a second-half brace from substitute Tolu Arokodare.
The result lifted the Super Eagles to second place in Group L with six points from three matches, one behind leaders Guinea-Bissau.
Chelle will look to the likes of Arokodare, Akor Adams, Simon and Moses Usor to provide the attacking firepower needed to secure another positive result.
Nigeria are scheduled to depart for Zanzibar on Sunday ahead of Tuesday's encounter at the Amaan Stadium.
