| First spacecraft to orbit Jupiter | 33 |
| First spacecraft to reach Uranus and Neptune | 44 |
| First spaceman | 14 |
| First spaceman's first name | 31 |
| First spacewoman | 16 |
| First Spanish actor to win an Oscar | 35 |
| First speaker in "Macbeth" | 36 |
| First specimen of a new species | 31 |
| First spin-off from "All in the Family" | 49 |
| First spin: mixed fruit | 23 |
| First spoken word in Genesis | 28 |
| First sporting company to sponsor an African-American | 53 |
| First sports commentator to receive an Emmy | 43 |
| First sports movie to win Best Picture | 38 |
| First square of some board games | 32 |
| First squirt of milk | 20 |
| First st. | 9 |
| First st. admitted to the union in the 20th century | 51 |
| First st. to join the Union after the end of the Civil War | 58 |
| First st. with women voters | 27 |
| First stabber of Caesar | 23 |
| First stage | 11 |
| First stage of a study | 22 |
| First stage of grief | 20 |
| First stages | 12 |
| First stakes | 12 |
| First star ever photographed, 1850 | 34 |
| First starter home? | 19 |
| First State | 11 |
| First state admitted to the Union from the Northwest Territory | 62 |
| First state capital | 19 |
| First state governor of Virginia | 32 |
| First State's capital | 25 |
| First State: Abbr. | 18 |
| First state? | 12 |
| First steamship to cross the Atlantic | 37 |
| First steamship with a planned circumnavigation of the globe | 60 |
| First Steely Dan album to win a Grammy | 38 |
| First step | 10 |
| First step for a would-be groom vis-Ã -vis his intended's father | 70 |
| First step in a hairdo | 22 |
| First step in a progression | 27 |
| First step in a series | 22 |
| First step in addicts' treatment | 36 |
| First step in division? | 23 |
| First step to riches? | 21 |
| First step toward nirvana | 25 |
| First step's span | 21 |
| First step? | 11 |
| First Stephen King novel | 24 |
| First steps | 11 |
| First stock sale, for short | 27 |
| First Stoic | 11 |
| First stomach of a cow | 22 |
| First stone thrower? | 20 |
| First strategy | 14 |
| First strategy choice | 21 |
| First string | 12 |
| First string? | 13 |
| First stringers | 15 |
| First strip to win a Pulitzer | 29 |
| First stroke for many | 21 |
| First stroke of a round | 23 |
| First stroke setting | 20 |
| First subclause | 15 |
| First subject in Euclid's "Elements" | 50 |
| First substitute on a basketball bench | 38 |
| First subway line in N.Y.C. | 27 |
| First subway line in NYC | 24 |
| First successful American automaker | 35 |
| First successful video game | 27 |
| First suit? | 11 |
| First Sum 41 hit | 16 |
| First Super Bowl M.V.P. | 23 |
| First Super Bowl MVP | 20 |
| First Super Bowl rematch | 24 |
| First Super Bowl that was actually called a Super Bowl | 54 |
| First Super Bowl to be officially called "Super Bowl" | 63 |
| First Super Bowl won by an African American coach | 49 |
| First Super Bowl won by the AFL | 31 |
| First Super Bowl won by the Giants | 34 |
| First supersonic human | 22 |
| First survey datum, often | 25 |
| First Syd Barrett solo album | 28 |
| First symbol on a music line | 28 |
| First symbol on a musical staff | 31 |
| First symptoms | 14 |
| First symptoms, e.g. | 20 |
| First synthetic dye | 19 |
| First T. Rex hit in 1970 | 24 |
| First talking pet in American comics | 36 |
| First Tarzan portrayer | 22 |
| First tea sold in individual packets | 36 |
| First team | 10 |
| First team to play in a domed stadium | 37 |
| First team to win five Super Bowls | 34 |
| First telegrapher | 17 |
| First temptation site | 21 |
| First tennis player to simultaneously hold Grand Slams on clay, grass and hardcourt | 83 |
| First tennis player to win more than a million dollars in a single season | 73 |