| First tribe met by Lewis and Clark | 34 |
| First tribe encountered by Lewis and Clark | 42 |
| First track on the 1956 album "Calypso" | 49 |
| First track on many a Broadway album | 36 |
| First track on a mix tape, usually | 34 |
| First Top 40 hit for Weird Al Yankovic | 38 |
| First Top 40 hit for "Weird Al" | 41 |
| First top 10 hit for Hall and Oates | 35 |
| First toothbrush to go to the moon | 34 |
| First to win 100 NCAA team championships | 40 |
| First to wake, according to Ovid | 32 |
| First to span the Atlantic wirelessly | 37 |
| First to show that men are pigs? | 32 |
| First to round the Cape of Good Hope | 36 |
| First to recognize the returning Odysseus | 41 |
| First to leave the table, perhaps | 33 |
| First to draw the Democrats' mule | 37 |
| First to draw Santa as he looks today | 37 |
| First to broadcast hockey play-by-play | 38 |
| First to attack in "The Birds" | 40 |
| First tight end in the Football Hall of Fame | 44 |
| First three-time heavyweight champ | 34 |
| First three-letter White House monogram | 39 |
| First three numbers, in some directories | 40 |
| First three community cards in hold'em | 42 |
| First third of a classic canine star's name | 47 |
| First things half of all newlyweds change? | 42 |
| First thing you do on December 25th | 35 |
| First thing usually hit by a bowling ball | 41 |
| First thing plucked in "Alouette" | 43 |
| First thing Iowa State cheerleaders ask for? | 44 |
| First thing in the water, usually | 33 |
| First thing Emory cheerleaders call for | 39 |
| First thing an Indiana cheerleader calls for | 44 |
| First these, then you get "to riches" | 47 |
| First The Wall Street Journal editor | 36 |
| First territorial capital of Alaska | 35 |
| First team to win five Super Bowls | 34 |
| First team to play in a domed stadium | 37 |
| First tea sold in individual packets | 36 |
| First talking pet in American comics | 36 |
| First Super Bowl won by the Giants | 34 |
| First Super Bowl won by an African American coach | 49 |
| First successful American automaker | 35 |
| First substitute on a basketball bench | 38 |
| First step in addicts' treatment | 36 |
| First Steely Dan album to win a Grammy | 38 |
| First steamship to cross the Atlantic | 37 |
| First state governor of Virginia | 32 |
| First star ever photographed, 1850 | 34 |
| First square of some board games | 32 |
| First sports movie to win Best Picture | 38 |
| First sports commentator to receive an Emmy | 43 |
| First spin-off from "All in the Family" | 49 |
| First speaker in "Macbeth" | 36 |
| First Spanish actor to win an Oscar | 35 |
| First spacecraft to reach Uranus and Neptune | 44 |
| First spacecraft to orbit Jupiter | 33 |
| First sovereign of Great Britain | 32 |
| First song on "More of the Monkees" | 45 |
| First Song of the Year Grammy winner | 36 |
| First son of a President to become President | 44 |
| First sitting president to visit the West Coast | 47 |
| First single released on Apple Records | 38 |
| First sign of a highway headache | 32 |
| First showing at an all-day film festival? (1988) | 49 |
| First Sherlock Holmes book: 1887 | 32 |
| First sergeant, in military slang | 33 |
| First section of a textbook, for short | 38 |
| First Secretary of Transportation | 33 |
| First secretary of Homeland Security | 36 |
| First secretary of H.E.W., 1953, ___ Culp Hobby | 47 |
| First Secretary General of the U.N. | 35 |
| First Sec. of Transportation: 1966 | 34 |
| First Scorsese/DeNiro collaboration | 35 |
| First Russian to be called "czar" | 43 |
| First Russian Literature Nobelist Ivan | 38 |
| First Russian Literature Nobelist | 33 |
| First round exemptions, in tournaments | 38 |
| First rock star to appear on a U.S. stamp | 41 |
| First right-handed batter to reach 500 home runs | 48 |
| First responders' destinations, briefly | 43 |
| First resident of the White House | 33 |
| First Republic of Texas president | 33 |
| First refugee named Canadian Prime Minister | 43 |
| First Reality Primetime Emmy winner | 35 |
| First razor with a pivoting head | 32 |
| First rapper to win a Best Song Oscar | 37 |
| First question at a start-up company? | 37 |
| First punch of an old Roman bout? | 33 |
| First Pulitzer Prize novelist: 1918 | 35 |
| First publisher of the game Mouse Trap | 38 |
| First published black woman poet in America | 43 |
| First pronoun in "Little Miss Muffet" | 47 |
| First pronoun in "America" | 36 |
| First pro team to play on artificial turf | 41 |
| First prize at the 1992 Olympics | 32 |
| First private engineering school in the U.S. | 44 |
| First priority of an Australian beverage company? | 49 |
| First prime minister of the U.S.S.R. | 36 |