Geraghty takes over the captaincy in the absence of George Skivington, who misses the match with a back injury.
Marland Yarde replaces Topsy Ojo on the wing after Ojo fractured his jaw in the victory over Newcastle last weekend.
James O’Connor has a hamstring injury and is replaced at full-back by Alex Lewington.
Irish director of rugby Brian Smith said: "We enjoyed a good win last weekend but have picked up a few injuries for our troubles.
"The players stepping in know they have big shoes to fill. Northampton will be a step up this weekend; Franklins Gardens is always a tough place to go so we know we will have to be at our best to compete.”
Matt Parr, Mike Mayhew and Leo Halavatau start in the front row for a second successive week with Kieran Low replacing Skivington in the second row to join Nic Rouse.
Gerard Ellis, who scored on his Premiership debut last week, will start in the back row with Blair Cowan and Ofisa Treviranus.
Tomas O’Leary and Geraghty will start at half back with Eamonn Sheridan and Fergus Mulchrone in the centre. Andrew Fenby, Yarde and Lewington make up the back three.
London Irish team to face Northampton Saints: 15. Alex Lewington; 14. Marland Yarde; 13. Fergus Mulchrone; 12. Eamonn Sheridan; 11. Andrew Fenby ; 10. Shane Geraghty (Captain); 9. Tomas O’Leary; 1. Matt Parr; 2. Mike Mayhew; 3. Leo Halavatau; 4. Kieran Low; 5. Nic Rouse; 6. Blair Cowan; 7. Gerard Ellis; 8. Ofisa Treviranus.
Replacements: 16. Jimmy Stevens; 17. Johnny Harris; 18. Jamie Hagan; 19. Bryn Evans; 20. Jebb Sinclair; 21. Tom Homer; 22. Ian Humphreys; 23. Darren Allinson.
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