| Major progress | 14 |
| Major Prophet | 13 |
| Major province in Afghanistan | 29 |
| Major publicity | 15 |
| Major publisher of romance novels | 33 |
| Major purchase | 14 |
| Major purchaser of McCain ads: Abbr. | 36 |
| Major racket | 12 |
| Major rant | 10 |
| Major rd. | 9 |
| Major rd. in Philly or San Francisco | 36 |
| Major rds. | 10 |
| Major recessions affect them | 28 |
| Major recipient of TARP money, which it paid back | 49 |
| Major record co. | 16 |
| Major record label | 18 |
| Major record label, once | 24 |
| Major reduction plan | 20 |
| Major ref. set | 14 |
| Major ref. work | 15 |
| Major region with a minor part? | 31 |
| Major report | 12 |
| Major Republican funder | 23 |
| Major responsibility for a parent? | 34 |
| Major retailer | 14 |
| Major rift | 10 |
| Major river of Spain | 20 |
| Major river to the Mediterranean | 32 |
| Major road | 10 |
| Major roads | 11 |
| Major role | 10 |
| Major role in "1776" | 30 |
| Major role in "Troy" | 30 |
| Major route | 11 |
| Major rte. | 10 |
| Major rtes. | 11 |
| Major ruckus | 12 |
| Major rug exporter | 18 |
| Major Russian ballet company, familiarly | 40 |
| Major Russian river | 19 |
| Major San Francisco industry, briefly | 37 |
| Major scale | 11 |
| Major scale in which B is the only natural | 42 |
| Major scale that has C as the seventh note | 42 |
| Major scale that has F as the third note | 40 |
| Major Scandinavian seaport | 26 |
| Major sch. events | 17 |
| Major school assignment | 23 |
| Major school of Buddhism | 24 |
| Major scoldings | 15 |
| Major scoop | 11 |
| Major screw-up | 14 |
| Major screwup | 13 |
| Major seaport in Va. | 20 |
| Major seaport of South Afr. | 27 |
| Major section of the "Seventy-Six Trombones" band | 59 |
| Major sector of the psyche | 26 |
| Major setback | 13 |
| Major shipbuilding city | 23 |
| Major shock | 11 |
| Major show | 10 |
| Major showcase | 14 |
| Major sight in the sky? | 23 |
| Major silicone manufacturer | 27 |
| Major silver exporter | 21 |
| Major skirmishes | 16 |
| Major source of baseball talent | 31 |
| Major source of the narcotic qat | 32 |
| Major span | 10 |
| Major Spanish daily | 19 |
| Major Spanish port city | 23 |
| Major Spanish river | 19 |
| Major spans | 11 |
| Major staff changes | 19 |
| Major star | 10 |
| Major start? | 12 |
| Major starter? | 14 |
| Major steps | 11 |
| Major stores | 12 |
| Major stories | 13 |
| Major stress factor, it's said | 34 |
| Major stretch | 13 |
| Major stretches | 15 |
| Major strikes | 13 |
| Major success | 13 |
| Major successor | 15 |
| Major suffix | 12 |
| Major suffix? | 13 |
| Major suit | 10 |
| Major suit, briefly | 19 |
| Major suit? | 11 |
| Major suits | 11 |
| Major supply | 12 |
| Major supporters of the ACA | 27 |
| Major surprise | 14 |
| Major swag | 10 |
| Major talent agcy. | 18 |
| Major target in Risk | 20 |
| Major tea source | 16 |
| Major tech stock | 16 |