Not necessarily- you can often still overclock a locked multiplier CPU based on other factors. For instance, I can overclock my 2600 non-k by raising the vcore and the BLCK, but this only gets me so far. I realize we're talking AMD here, but the concept still applies to both camps.
Yes, the easiest way is to use an unlocked mutli, but this also depends on what CPU family, MB chipset and BIOS settings you have at your disposal.