Released by the Democratic Alliance in Cape Town on Thursday, it says Zuma has failed both his office and South Africa, "and should no longer be entrusted with the presidency".
Briefing the media on the report's content, parliamentary leader Lindiwe Mazibuko said Zuma had "failed comprehensively to provide effective leadership in government".
She cited government's "lacklustre response" to events at Marikana earlier this year, the so-called Nkandlagate scandal, and the country's "lack of economic policy direction", among reasons for his scoring an F.
These issues, and others, had also been what had motivated the DA, along with seven other opposition parties, to table a motion of no-confidence in Zuma last month.
Mazibuko said Zuma's score "stands in contrast to Deputy President Kgalema Motlanthe, who we have awarded a C".
Mazibuko said that while Motlanthe was not the top performer in Cabinet, he had "displayed noteworthy qualities which President Zuma clearly lacks".
These included a dedication to the Constitution, an honest approach to the serious challenges facing government, and a willingness to engage openly with Parliament and South Africans.
At the briefing, the DA's Wilmot James singled out Agriculture, Forestry and Fisheries Minister Tina Joemat-Pettersson for special mention.
"It is worth acknowledging separately the quite disastrous and embarrassing tenure of [this minister], who... received an F.
"Her handling of almost every single matter before her has been so incompetent and negligent that there is no longer any doubt that she should be removed from Cabinet without any further delay."
James later told journalists that when it came to Joemat-Pettersson, if the DA's grading system -- which runs from A to F -- had gone below an F, "we would have considered that as well".
Other ministers in the 34-member Cabinet who scored an F include Minister in the Presidency Collins Chabane, Labour Minister Mildred Oliphant, Police Minister Nathi Mthethwa, and State Security Minister Siyabonga Cwele.
Top 2012 performers were Health Minister Aaron Motsoaledi and then Science and Technology Minister Naledi Pandor (who moved to home affairs late in the year), who both received an A.
On Motsoaledi, the report finds that under his leadership, the health department has "achieved significant successes in the fight against HIV/Aids".
On Pandor, it says she had performed "an admirable job of setting and pursuing a clear vision for science and technology in South Africa".