The 1557 influenza pandemic spread from Asia to the Ottoman Empire, then Europe, the Americas, and Africa. This flu pandemic is the first to be reliably recorded as spreading worldwide,^[3][4][5][6] is when flu received its first English names.^[7][8] It is also the first pandemic in which flu is linked to miscarriages.^[9] The pandemic lasted for at least two years.^{[10]: 307–308 [11]}

The 1580 pandemic is well-documented, with high mortality recorded as influenza spreads across Europe.^[12]

The disease seems to have been present in the northeast United States as early as October 1732, after which reports of it came out of Newfoundland, Barbados, Jamaica, Mexico, Peru, and Chile.^{[13]: 9 [30]: 23} The following month it appeared in Germany, reportedly coming from Russia through Poland.^[30]: 23 It spread throughout Germany in November and into December, when it caused outbreaks in Switzerland and Holland through the end of the year.^[30]: 23 Notably, it was reported on the Isle of Bourbon, off of Madagascar, in December as well.^[13]: 9 It prevailed in London and Paris in January 1733, as well as the Netherlands; that same month, it was reported in Italy, where it continued into March.^[13]: 9 Madrid was visited in February.^[13]: 9

Though the name had been used in English before, this was the first time "influenza" was broadly used to refer to the disease. While it prevailed extensively in Italy, the rumor of a "great epidemic" of "influenza" in that country spread faster than the disease itself, and the name came to be used in England, at least for the duration of the outbreak. Once it had passed, the name fell out of common use.^[10]: 304

On the whole, the epidemic was notable for seeming to follow no clear path, "being reported now here, now there,"^[30]: 27 and for missing certain locales altogether, such as Paris.^[10]: 358 Morbidity was "great" where the disease did strike.^[30]: 27 Mortality was relatively low, though it did vary, with some cities seeing more severe epidemics than others even within the same country.^{[30]: 27 [10]: 358} Spontaneous abortions and premature births were reported as new complications during this pandemic, which can be taken as a piece of supporting evidence that this was indeed a pandemic of influenza, in addition to its high attack rate and broad distribution across at least two continents.^{[30]: 27 [37]}

Other authors, however, consider only the 1781–1782 experience to be a true pandemic.^{[13]: 18 [30]: 30 [15]: 27} If anything, the outbreaks in Russia and North America in 1780–1781 were possible "herald waves" of the later, greater epidemic.^[15]: 27 During this true pandemic period, influenza is said to have first broken out in China and British India in the fall of 1781.^[13]: 11 By the winter, it was sweeping through Siberia and Russia, visiting St. Petersburg again in January 1782.^[13]: 11 It moved through Germany between February and June.^[13]: 11 It struck Finland in February and Denmark, Sweden, and Hungary in April. After reaching England as early as April, influenza broke out in London and other parts in May and was general in England and Scotland in June.^[13]: 11 After hitting the Netherlands in May, it spread to France and then to Italy, where it broke out in June.^[30]: 30 Finally, it reached Spain by August, prevailing in Madrid and other parts.^[13]: 11

This epidemic solidified "influenza" as the name of the disease in English. Although first used generally in 1743 to refer to the affliction epidemic in Italy at the time, it was not until an epidemic in 1775 that the term began to be used again more generally, and by 1782, it was the typical name applied. In the summer of that year, when the disease hit England, the Royal College of Physicians formally adopted the Italian word as the official name.^[10]: 362

The influenza was first reported in Russia in March 1788, in St. Petersburg and Kherson and in Poland.^[13]: 11 It then spread westward, invading Germany, Hungary, Denmark, England, Scotland, France, and Italy successively throughout the year and being reported finally in Switzerland in October.^[13]: 11 Observed influenza activity then remained low for nearly a year before the disease appeared in the Western Hemisphere, breaking out in the US states of Georgia and New York in September 1789.^[13]: 11 The epidemic crossed the entire United States in six to eight weeks.^[42]: 290 It was reported in Jamaica in October^[13]: 11 and Grenada in November,^{[43]: 256–257} and by the end of the year it was prevalent in Nova Scotia and South America.^[13]: 11 After a short reprieve, the influenza resumed epidemic proportions in the spring of 1790 in the northeast United States and perhaps some other parts,^[13]: 12 declining about the first week of June.^[43]: 259 There is some evidence of increased severity during the spring wave as compared to the fall one.^[42]: 291 The disease was prevalent again in Philadelphia and neighboring counties in Pennsylvania, and was observed as well in Virginia and Rhode Island, in the winter of 1790–1791, but it was not nearly as widespread as its first two appearances.^[43]: 260