| First single released on Apple Records | 38 |
| First sin site | 14 |
| First Sikh | 10 |
| First signs of rain | 19 |
| First signs | 11 |
| First sign, astrologically | 26 |
| First sign of the zodiac | 24 |
| First sign of spring? | 21 |
| First sign of spring | 20 |
| First sign of rain | 18 |
| First sign of fall | 18 |
| First sign of a highway headache | 32 |
| First sign | 10 |
| First side to vote | 18 |
| First shows | 11 |
| First showings | 14 |
| First showing of a film | 23 |
| First showing at an all-day film festival? (1988) | 49 |
| First showing | 13 |
| First show | 10 |
| First shots in billiards | 24 |
| First shot, for many | 20 |
| First shot | 10 |
| First Shia imam | 15 |
| First Sherlock Holmes book: 1887 | 32 |
| First shepherd in the Bible | 27 |
| First shepherd | 14 |
| First sheepkeeper | 17 |
| First sgt., e.g. | 16 |
| First settlers | 14 |
| First set of wheels, maybe | 26 |
| First sergeants, to G.I.'s | 30 |
| First sergeant, informally | 26 |
| First sergeant, in military slang | 33 |
| First sergeant | 14 |
| First sequel to win Best Picture, with "The" | 54 |
| First senator in space | 22 |
| First semester offerings | 24 |
| First self-propelled spaceman | 29 |
| First self-propelled astronaut | 30 |
| First seducer | 13 |
| First section of a tome | 23 |
| First section of a textbook, for short | 38 |
| First section | 13 |
| First secretary of war | 22 |
| 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 second son | 16 |
| First Sec. of Transportation: 1966 | 34 |
| First season | 12 |
| First Seahawk quarterback Jim | 29 |
| First Scorsese/DeNiro collaboration | 35 |
| First schizophrenic problem? | 28 |
| First schizophrenicproblem? | 28 |
| First sch. to win 100 NCAA championships, across all sports | 59 |
| First sch. | 10 |
| First satellite to transmit a phone call through space, 1962 | 60 |
| First satellite | 15 |
| First saint canonized by a pope | 31 |
| First Russian tsar | 18 |
| First Russian to orbit Earth | 28 |
| First Russian to be called "czar" | 43 |
| First Russian Orthodox saint | 28 |
| First Russian Literature Nobelist Ivan | 38 |
| First Russian Literature Nobelist | 33 |
| First Russian czar | 18 |
| First rung on a ladder | 22 |
| First run of the still | 22 |
| First ruler of the Slavs | 24 |
| First ruler of all Egypt | 24 |
| First rule of lion taming? | 26 |
| First row | 9 |
| First round pick of the Magic | 29 |
| First round of voting | 21 |
| First round exemptions, in tournaments | 38 |
| First round draft pick, perhaps | 31 |
| First roofed ballpark | 21 |
| First romance, often | 20 |
| First Roman to be deified | 25 |
| First Roman emperor | 19 |
| First rock star to appear on a U.S. stamp | 41 |
| First rock from the sun | 23 |
| First rock band whose members received Kennedy Center Honors | 60 |
| First rite | 10 |
| First right-handed batter to reach 500 home runs | 48 |
| First rib-loser | 15 |
| First response to a call | 24 |
| First response orgs. | 20 |
| First responders: Abbr. | 23 |
| First responders, often (abbr.) | 31 |
| First responders, for short | 27 |
| First responders, briefly | 25 |
| First responders, at times | 26 |
| First responders' destinations, briefly | 43 |
| First responders (abbr.) | 24 |
| First responder, say: Abbr. | 27 |
| First responder, perhaps | 24 |
| First responder, often | 22 |