| First American auto company | 27 |
| First American baseball stadium with a retractable roof | 55 |
| First American canal | 20 |
| First American diplomat abroad | 30 |
| First American executed for spying | 34 |
| First American female astronaut | 31 |
| First American in orbit | 23 |
| First American in space | 23 |
| First American independent movie to get a Best Original Screenplay nomination | 77 |
| First American literature Nobelist | 34 |
| First American magazine to excerpt "Moby-Dick" | 56 |
| First American minister to England | 34 |
| First American movie to show a toilet flushing | 46 |
| First American orbiter | 22 |
| First American Railway Union president | 38 |
| First American Red Cross president Barton | 41 |
| First American saint | 20 |
| First American steam locomotive | 31 |
| First American to orbit Earth | 29 |
| First American to orbit the Earth | 33 |
| First American to walk in space | 31 |
| First American to win the Tour de France | 40 |
| First American Tour de France winner Greg | 41 |
| First American woman in space | 29 |
| First among men | 15 |
| First among progeny | 19 |
| First among siblings | 20 |
| First among the children | 24 |
| First and bulldog | 17 |
| First and foremost | 18 |
| First and foremost: Abbr. | 25 |
| First and last digit in a Manhattan area code | 45 |
| First and last name of an author | 32 |
| First and last quarters, e.g. | 29 |
| First and last word of a W. S. title | 36 |
| First and last word of the Musketeers' motto | 48 |
| First and only fictional group to have a #1 hit song, with "The" | 74 |
| First and pocket | 16 |
| First and reverse, e.g. | 23 |
| First and second | 16 |
| First and second for example | 29 |
| First and Second Avenues area, in Manhattan | 43 |
| First and Second places? | 24 |
| First and second, e.g. | 22 |
| First and second, for two | 25 |
| First and third | 15 |
| First and ___ (football term) | 29 |
| First animal in the Chinese zodiac | 34 |
| First animal shelter | 20 |
| First animal, in a way | 22 |
| First animal? | 13 |
| First anniversary gift | 22 |
| First Annual Grammy Awards host Mort | 36 |
| First anti-AIDS drug | 20 |
| First apartment, perhaps | 24 |
| First appearance | 16 |
| First appearance, as of symptoms | 32 |
| First appearances | 17 |
| First apple polisher? | 21 |
| First application blank | 23 |
| First application line to fill in | 33 |
| First Arab country to have sanctions imposed on it by the Arab League | 69 |
| First Arabic letter | 19 |
| First arboretum | 15 |
| First area to fill in on a form | 31 |
| First Army first name | 21 |
| First arrival | 13 |
| First Arthur C. Clarke Award winner | 35 |
| First artificial satellite | 26 |
| First Asian city to host the Winter Olympics | 44 |
| First Asian country to rule in favor of same-sex marriage | 57 |
| First Asian-American Cabinet member | 35 |
| First aspirin maker | 19 |
| First assembly-line carmaker | 28 |
| First asteroid | 14 |
| First asteroid discovered | 25 |
| First asteroid ever discovered | 30 |
| First asteroid landed on by a NASA craft | 40 |
| First asteroid landed on by a spacecraft | 40 |
| First asteroid orbited by a NASA spacecraft | 43 |
| First athlete to appear on the cover of Time magazine | 53 |
| First athlete to lend his name to a video game | 46 |
| First attempt | 13 |
| First attempts? | 15 |
| First author of the "Oz" books | 40 |
| First authority | 15 |
| First auto to offer seat belts | 30 |
| First baby picture, often | 25 |
| First baby picture, perhaps | 27 |
| First ballplayer to hit 50 home runs before the end of August | 61 |
| First band, alphabetically, on many an iPod | 43 |
| First base man? | 15 |
| First base? | 11 |
| First baseball commissioner | 27 |
| First baseball czar | 19 |
| First baseball Hall of Famer | 28 |
| First Baseball Hall-of-Famer, alphabetically | 44 |
| First baseball player involved in an instant replay decision | 60 |
| First baseball player to have his number retired | 48 |
| First baseball player to make $1 million a year | 47 |