| First two-time Nobelist | 23 |
| First two-Nobel winner | 22 |
| First two words of a 1964 Impressions hit | 41 |
| First two words of "Waltzing Matilda" | 47 |
| First two words of "Green Eggs and Ham" | 49 |
| First two words of "Dixie," often | 43 |
| First two words of "A Tale of Two Cities" | 51 |
| First two segments of a famous Nintendo cheat code | 50 |
| First two reindeer named in Rudolph's song | 46 |
| First two of "three little words" | 43 |
| First two notes of a descending scale | 37 |
| First two in the first garden | 29 |
| First two | 9 |
| First TV western series | 23 |
| First TV superstar Milton | 25 |
| First TV show to debut at #1 in the Nielsen ratings | 51 |
| First TV show | 13 |
| First TV series to show a baby being born, 1955 | 47 |
| First TV appearance | 19 |
| First Tudor king | 16 |
| First tuba note? | 16 |
| First tsar of Russia | 20 |
| First Triumvirate member | 24 |
| First Triumvirate foe | 21 |
| First Triple Crown winner | 25 |
| First trick | 11 |
| First tribe met by Lewis and Clark | 34 |
| First tribe encountered by Lewis and Clark | 42 |
| First Treasury secretary | 24 |
| First treasure found in "Raiders of the Lost Ark" | 59 |
| First transplant recipient | 26 |
| First trail | 11 |
| First track, often | 18 |
| 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 track off Scorpions' "Crazy World" | 54 |
| 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 vote | 13 |
| First to twelth, e.g. | 21 |
| First to Third, in Germany | 26 |
| First to take up arms | 21 |
| First to take a ribbing | 23 |
| First to swim Lake Ontario | 26 |
| First to strike Caesar | 22 |
| First to stab Caesar | 20 |
| First to spot a comet, usually | 30 |
| First to span the Atlantic wirelessly | 37 |
| First to show that men are pigs? | 32 |
| First to sell out | 17 |
| First to see the sun, maybe | 27 |
| First to second, for one | 24 |
| First to round the Cape of Good Hope | 36 |
| First to respond, often (abbr.) | 31 |
| First to recognize the returning Odysseus | 41 |
| First to putt | 13 |
| First to move in chess | 22 |
| First to leave the table, perhaps | 33 |
| First to leave the blocks | 25 |
| First to flood? | 15 |
| First to draw the Democrats' mule | 37 |
| First to draw Santa as he looks today | 37 |
| First to come? | 14 |
| First to come | 13 |
| First to broadcast hockey play-by-play | 38 |
| First to break the tape | 23 |
| First to be counted? | 20 |
| First to be counted | 19 |
| First to be chosen | 18 |
| First to be called up | 21 |
| First to be called | 18 |
| First to be admitted?: Abbr. | 28 |
| First to bat | 12 |
| First to attack in "The Birds" | 40 |
| First to arrive? | 16 |
| First to arrive, often: Abbr. | 29 |
| First to arrive | 15 |
| First time out | 14 |
| First tiller or killer | 22 |
| First tiller | 12 |
| First tight end in the Football Hall of Fame | 44 |
| First tight end elected to the Pro Football Hall of Fame | 56 |
| First three-time heavyweight champ | 34 |
| First three-letter White House monogram | 39 |
| First three of five | 19 |
| First three numbers, in some directories | 40 |
| First three kinds of holes | 26 |
| First three community cards in hold'em | 42 |
| First three colors of rainbow | 29 |
| First thought of | 16 |
| First third of an out | 21 |
| First third of a classic canine star's name | 47 |
| First things learned | 20 |
| First things half of all newlyweds change? | 42 |
| First things | 12 |