The 27-year-old Team Sky cyclist - the Olympic time-trial bronze medalist and second in last year's Tour de France - had 54 seconds to spare over second-placed Slovenian Simon Spilak while Portugal's Rui Costa filled third spot just as he did last year.
Germany's time-trial specialist Tony Martin displayed his expertise in the discipline by winning Sunday's final stage in Geneva.
Froome, already winner this season of the Tour of Oman and the International Criterium, will hope he goes on and replicates the Tour de France success of the past two winners of this race, Australia's Cadel Evans in 2011 and the Briton's compatriot and Sky team-mate Bradley Wiggins last year.
Results on Sunday from the sixth and final day of the Tour of Romandie, a 18.7km time trial stage:
1. Tony Martin, Germany, Omega Pharma-Quick Step, 21 minutes, 7 seconds.
2. Adriano Malori, Italy, Lampre-Merida, 16 seconds behind.
3. Chris Froome, Britain, Sky, 0:34.
4. Lieuwe Westra, Netherlands, Vacansoleil-DCM, 0:36.
5. Simon Spilak, Slovakia, Katusha, 0:41.
6. Stef Clement, Netherlands, Blanco, 0:50.
7. Richie Porte, Australia, Sky, 0:52.
8. Mads Christensen, Denmark, Saxo-Tinkoff, 0:55.
9. Rohan Dennis, Australia, Garmin Sharp, 0:56.
10. Tobias Ludvigsson, Sweden, Argos-Shimano, 1:01.
Final standings (After 6 stages)
1. Chris Froome, Britain, Sky, 19 hours, 24 minutes, 51 seconds.
2. Simon Spilak, Slovakia, Katusha, 54 seconds behind.
3. Rui Costa, Portugal, Movistar, 1:49.
4. Tom Danielson, United States, Garmin Sharp, 1:54.
5. Wilco Kelderman, Netherlands, Blanco, 2:03.
6. Jean-Christophe Peraud, AG2R La Mondiale, France, 2:14.
7. Jurgen van den Broeck, Belgium, Lotto Belisol, 2:16.
8. Richie Porte, Australia, Sky, 2:31.
9. Alejandro Valverde, Spain, Movistar, 2:32.
10. Marcel Wyss, Switzerland, IAM, 2:41.