| Sega Bass Fishing | Wii | 1999 | Sega Wow |
| Sega Soccer Slam | Nintendo GameCube | 2002 | EA Jawbreaker |
| Sega Superstars Tennis | Wii | 2008 | Sumo Digital |
| Seicross | Nintendo Entertainment System | 1984 | Nichibutsu |
| Seifuku Densetsu Pretty Fighter | Super Nintendo Entertainment System | 1994 | Genki |
| Seijuu Maden: Beasts & Blades | Super Nintendo Entertainment System | 1996 | — |
| Seikima II Akuma no Gyakushū! | Nintendo Entertainment System | 1986 | ISCO |
| Sekiryūō | Nintendo Entertainment System | 1989 | Sunsoft |
| Sengoku | Super Nintendo Entertainment System | 1991 | SNK |
| Sengoku Basara 2 | Wii | 2006 | Capcom |
| Sengoku Basara 3 Utage | Wii | 2011 | Capcom |
| Senran Kagura 2: Deep Crimson | Nintendo 3DS | 2014 | Tamsoft |
| Senran Kagura Burst | Nintendo 3DS | 2018 | Tamsoft |
| Senran Kagura: Skirting Shadows | Nintendo 3DS | 2011 | Tamsoft |
| Sensible Soccer | Super Nintendo Entertainment System | 1992 | Sensible Software |
| Serious Sam: Next Encounter | Nintendo GameCube | 2004 | Climax Studios |
| Serpent | Game Boy | 1990 | Kaga Create |
| Sesame Street Countdown | Nintendo Entertainment System | 1992 | Running with Scissors |
| Sesame Street Letters | Nintendo Entertainment System | 1989 | Rare Ltd. |
| Sesame Street: A-B-C/1-2-3 | Nintendo Entertainment System | 1991 | Rare Ltd. |
| Sesame Street: Numbers Count | Nintendo Entertainment System | 1989 | Rare Ltd. |
| Severed | PlayStation Vita, Nintendo 3DS | 2016 | Drinkbox Studios |
| Sexy Poker | Wii | 2009 | Gameloft |
| Sgt. Saunders' Combat! | Super Nintendo Entertainment System | 1995 | — |
| Shadow Brain | Nintendo Entertainment System | 1991 | Scitron & Art Inc. |
| Shadow of the Beast | Super Nintendo Entertainment System | 1989 | Ubisoft Reflections |
| Shadow of the Ninja | Nintendo Entertainment System | 1990 | Winning Entertainment Group |
| Shadow the Hedgehog | Nintendo GameCube | 2005 | Sega |
| Shadowgate | Nintendo Entertainment System | 1987 | ICOM Simulations |
| ShadowPlay | Wii | 2010 | Deep Fried Entertainment |
| Shadowrun | Super Nintendo Entertainment System | 1993 | Krome Studios Melbourne |
| Shake It Up | Wii | 2011 | Papaya Studio |
| Shake It Up 2: Groove It Up | Wii | 2012 | Papaya Studio |
| Shakedown: Hawaii | PlayStation Vita, Nintendo 3DS, Wii | 2019 | Vblank Entertainment |
| Shaman King: Soul Fight | Nintendo GameCube | 2003 | — |
| Shamu's Deep Sea Adventures | Nintendo GameCube | 2005 | Activision |
| Shamus | Game Boy | 1982 | — |
| Shanghai | Nintendo Entertainment System | 1986 | Sunsoft |
| Shanghai III | Super Nintendo Entertainment System | 1993 | Success, Kuusoukagaku, Sunsoft |
| Shantae | Nintendo 3DS | 2002 | WayForward Technologies |
| Shantae and the Pirate's Curse | Nintendo 3DS | 2014 | WayForward Technologies |
| Shaq Fu | Super Nintendo Entertainment System, Game Boy | 1994 | Delphine Software International |
| Shark Tale | Nintendo GameCube | 2004 | Edge of Reality |
| Shatterhand | Nintendo Entertainment System | 1991 | Winning Entertainment Group |
| Shaun White Skateboarding | Wii | 2010 | Ubisoft Montreal |
| Shaun White Snowboarding | Wii | 2008 | Ubisoft Montreal |
| Shaun White Snowboarding: Road Trip | Wii | 2008 | 2K China |
| Shaun White Snowboarding: World Stage | Wii | 2009 | Ubisoft Montreal |
| Sherlock Holmes and the Mystery of the Frozen City | Nintendo 3DS | 2012 | Frogwares |
| Sherlock Holmes: Hakushaku Reijō Yūkai Jiken | Nintendo Entertainment System | 1986 | Towa Chiki |
| Sherlock Holmes: The Mystery of the Mummy | Wii | 2002 | Frogwares |
| Shien's Revenge | Super Nintendo Entertainment System | 1994 | Givro |
| Shifting World | Nintendo 3DS | 2012 | — |
| Shigetaka Kashiwagi's Top Water Bassing | Super Nintendo Entertainment System | 1995 | — |
| Shijō Saikyō League Serie A: Ace Striker | Super Nintendo Entertainment System | 1995 | — |
| Shikinjoh | Nintendo Entertainment System | 1991 | Sunsoft |
| Shimano Xtreme Fishing | Wii | 2009 | EV Interactive |
| Shin Kidō Senki Gundam Wing: Endless Duel | Super Nintendo Entertainment System | 1996 | Winning Entertainment Group |
| Shin Megami Tensei | Super Nintendo Entertainment System | 1992 | Atlus |
| Shin Megami Tensei If… | Super Nintendo Entertainment System | 1994 | Atlus |