The 27-year-old, who has 14 international caps with Spain, makes the move to the Etihad Stadium in a deal believed to be worth around £24 million.
Negredo, who will wear the number nine shirt last used by Emmanuel Adebayor, becomes new Citizens boss Manuel Pellegrini third recruit of the summer, following the arrival of former Sevilla team-mate Jesus Navas and Fernandinho from Shakhtar Donetsk.
Manchester City have been swift in getting their business done so far in this transfer window, and should further bolster their forward ranks with a deal for Fiorentina's Stevan Jovetic expected to be completed in the coming days.
The Montenegrin said he was 'thrilled' that his switch the the Citizens was close to being done yesterday, while Fiorentina's official Twitter account posted: "An agreement has been reached with Manchester City Football Club for the permanent sale of the player Stevan Jovetic."
The 23-year-old is also expected to cost City in the region of £24 million.